Immune Treatments


These treatments intend to treat cancer and other diseases by modifying immune function.

Albarin, Injectable Aloe Vera or Polymannons




To: "Health Freedom, Codex Issues
From: John Hammell
Date: Tue, 6 Nov 2001 13:43:35 -0500 (EST)

IAHF Webmaster: Breaking News, Create New Category: FDA ALBARIN RAIDS

IAHF LIST: The reason you haven't heard from me lately is because I am on the road in St.Petersburg FL assisting The Medical Center for Preventive and Nutritional Medicine of Tampa/St.Pete which got raided by the FDA Oct.11 placing several patients lives in jeopardy.In this article you will learn of the suppression of a remarkable injectable aloe vera treatment. Please help by taking the action steps requested at the end of my article.Please forward this to more people, and if you can help get Joe DiStephano on the air, please let me know. Urgent legal donations are needed by the clinic.


By John C. Hammell, President, International Advocates for Health Freedom POB 625 Floyd V A 24091 USA 800-333-2553

On October 11,2001 120 terrorists from the Food and Drug Administration, Florida Department of Law Enforcement, and the Hillsborough County Sheriff's Office raided alternative cancer clinics in Tampa and St.Petersburg Florida run under the auspices of The Medical Center for Preventative and Nutritional Medicine. Ironically, the raids came exactly one month after the terrorist attack on the World Trade Center/Pentagon, they were conducted by our own government.

What sets this raid apart from other FDA raids is that 80 % of the cancer patients coming to the clinics for treatment with Albarin, an injectable form of Aloe Vera, were going into remission and not a single complaint came from a patient. The only complaints came from mainstream oncologists obviously solely interested in protecting their economic turf. Many patients lives have been thrown into disarray and several will be dead within a month if they can't get their Albarin back.

If the FDA succeeds in this outrageous effort to suppress patient's access to Albarin, consumers may never again have access to any unapproved treatment they may wish to use, no matter how good it may be. It is essential that everyone take the actions suggested at the end of this article to defend the lives of the patients.

Along with the Tampa and St.Petersburg clinics, the FDA raided the home of Joseph DiStefano, the licensed nutrition counselor who ran them in conjunction with Daniel Mayer, D.O. Their first 100 patients all came from Hospice where they'd been told they only had 2-3 months to live.DiStefano and Mayer only lost 6 out of lOO of them.

Although Albarin is not an FDA approved drug, DiStefano and Mayer had been conducting an INR investigation for its developer, Ivan Danhof, MD, PhD of the N Texas Research Laboratory, Grand Prairie, TX into its uses in the treatment of pain in prostate cancer. Danhof had filed an application for an Investigational New Drug (IND) and was on the verge of providing the FDA with data to support this application, when the raid occurred. They were prepared with solid clinical data from over 30 patients charts to prove that Albarin has a powerful immune enhancing effect while blocking the blood supply to cancer cells, causing rapid diminishing of their size and killing them.

Instead of storming in with this raid which is now jeopardizing lives, the FDA should have simply visited the clinics for the sake of friendly communication to find out what DiStefano, Mayer and Danhof were doing to make sure they were acting in compliance with the law. By conducting this Nazi styled raid, the FDA has grossly violated their mandate to safeguard the public health and they've betrayed our trust. Instead of protecting the public in this case, their actions are directly threatening people's lives.

US Attorney's Office spokesman Steve Cole would not comment on the investigation and U.S. Judge Thomas Mc Coun III sealed the search warrant affidavits used to justify the search warrants for 120 days, as the government seeks to cook up some "justification" for this illegal fishing expedition.

Judging from what was said during the raid, the trumped up charges will most likely include dispensing unapproved drugs, and for Joe DiSteffano, practicing medicine without a license. This charge against DiSteffano is absurd because he has never held himself out to be a doctor, he's been legally working for 38 years as a licensed nutrition counselor always alongside a licensed medical practitioner, in this case, Mayer, an osteopath.

DiSteffano's patients know he is not a doctor, but many of them affectionately call him "Dr Joe" as a term of respect and appreciation. I didn't meet a single unhappy patient here, they all have nothing but praise for DiSteffano and Mayer stating that they don't charge a cent for their initial consultations, and only charge $1100 for Albarin treatment, no matter how many times they have to come back for treatments and they have always been quite willing to work with their patients financially, turning NO ONE away due to any inability to pay. ($1100. is far less than what mainstream oncologists typically charge for a weeks worth of chemotherapy.)

DiStefano and Mayer are without question two of the kindest, most altruistic men I've ever met. Now that they have been raided, they're in desperate need of donations for their legal fund because they aren't making much money at all running these clinics where the primary focus has been to simply help people, not to make money.

Paul Schebell, Margaret Marsh, Karen Kyper, Ruth Hannah, Will Weinand, James Strickland, Robert Banks, and Robert Scofield are among the terminally ill cancer patients who have just been issued death sentences by the Food and Drug Administration Their medical records were seized in the raid, along with Albarin, and your help is urgently needed to defend their lives in the face of this insanity. They could all be dead soon unless they can resume Albarin treatment.


This FDA fishing expedition began a week before the raid when DiStefano exited his office at midnight only to catch FDA Senior Special Agent Rande Mattison and another FDA accomplice trespassing on clinic property, illegally rummaging through his dumpster with rubber gloves on. Trespassing this way was an immense screw up on the part of Mattison who failed to notice DiStefano's car parked in the clinic parking lot and so wrongly believed no one was there.

When DiStefano demanded to know what they thought they were doing trespassing on his property, they had the nerve to tell him they were merely "searching for boxes." "Sure you are, with rubber gloves on at midnight- everyone ALWAYS looks for boxes with rubber gloves on at midnight, you can't legally come on my property without a search warrant, do you have one?" DiStefano proceeded to write down their license plate number while telling them he was going to call the police. "Good" Mattison sneered. They were about to drive away when DiStefano demanded that they put back all the garbage they had removed from the dumpster, but Mattison scowled and tersely informed him that they didn't have to, but his partner said "yes, we do" and he put all the garbage back. Mattison peeled out of the driveway. On the day of the raid in which all Albarin, and patients charts were seized, Mattison pulled DiSteffano aside and told him they were going to "get him" for "practicing medicine without a license."


Shortly before the raid, when DiStefano attempted to mail over 30 patient charts with carefully presented data intended to be used by Ivan Danhof, MD, PhD the Texas researcher who had spent over 30 years developing Albarin to apply for a compassionate use IND, the box was mysteriously RETURNED to him marked "refused by addressee." Danhof never received the package, and he and DiStefano now speculate that the FDA may have been monitoring their mail and that they may have blocked Danhof's receipt of the data as part of their ongoing effort to block public access to this highly successful alternative cancer treatment.

DiSteffano's mail was routinely 3 days late in arriving, and took an extra 3 days to be sent anywhere. His mailman told him that it was being held, but he didn't know why.

Will this terrorist attack soon be another documented case of government genocide as the FDA continues to flaunt their mandate to protect the public health while providing a protection racket defending the profits of such mainstream oncology centers as the Moffitt Cancer Center in Tampa Florida?

A week ago I flew to Tampa from Virginia on the urgent request of the Life Extension Foundation to write this article and to do anything possible to assist in the fight back. Having interviewed several patients, and reviewed their medical records, I am horrified by what the FDA has done here. Every Wednesday since the raid, DiStefano's patients have held rallies in front of the Federal Courthouse in Tampa, and I went with them last Wednesday to take pictures and help carry a sign reading "FDA- Give Us Our Albarin Back" Unless the Courts and Congress rapidly intercede to restore these patients access to Albarin, many patients will be dead quite soon, and many more others who had gone into complete remission will see their cancers return.


Ivan Danhof; MD, PhD, the developer of Albarin, is regarded by many to be the leading authority on the aloe vera plant. Working out of the North Texas Research Laboratory in Grand Prairie, TX, Danhof has impeccable credentials B.S in biochemistry, M.S in Nutrition and Microbiology, PhD in Physiology, and an MD with specialties in Internal Medicine and Gastroenterology. He has written 80 research papers throughout his career. Additionally, he has served as a Fulbright scholar in Afghanistan investigating Botanical medicine.

Danhof states that the Aloe Vera mucilaginous polysaccharide is a long chain sugar molecule composed of individual mannose and glucose sugar molecules connected together. There is a wide range in the size of the mucilaginous polysaccharide molecule, and their size determines their healing properties. Albarin consists of very large particles. up to 9000 molecules which are extracted through a patented freeze drying process turning them into a powder, which was then turned into an intravenously applied liquid by a compounding pharmacist. These large molecules are immune modulating, and have a very powerful healing effect on AIDS, Cancer, and many other immune system disorders. This large molecule also causes the body to produce a natural chemical tumor necrosis factor that functions to shut off the blood supply to tumors.

Illustrating the wide range of healing applications of aloe, Danhof states that the small particles. 60-600 molecules reduce inflammation- which is involved in such diseases as ulcerative colitis, arthritis, and gastric reflux. The small particles also help with the reduction of blood sugar in Type I and II diabetes.

Medium sized particles, up to 1500 molecules, are very effective intracellular antioxidants and free radical scavengers. Whereas vitamins and minerals only have antioxidant properties outside the cells, aloe works within the cells to prevent and treat arteriosclerosis, heart disease, and Parkinson's disease. With the ever increasing pollution of the soil, the increase in free radicals and loss of cellular oxygen will only get worse over time. This makes Aloe Vera mucilaginous polysaccharides more important than ever.

Large sized particles, up to 5000 molecules have a direct antibacterial and anti viral effect. This is important with all the new infectious diseases cropping up and older ones becoming more virulent from long term use of antibiotics.

As stated above, the Albarin serum is derived from the largest particles, up to 9000 molecules in size.


The mucilaginous polysaccharide molecule is very fragile. When the leaf of the aloe plant is cut, enzymes in the plant are released, which breaks down the long chain sugars of the mucilaginous polysaccharide into simple sugars, which then results in a loss of the different healing properties. There are very few products on the market that can claim to contain stabilized mucilaginous polysaccharides. Stabilization requires extraction of the musilaginous polysaccharides in a freeze-dried form but also the process must include a way to deactivate the enzymes released in the plant when it is cut. Furthermore, the high concentration of mineral salts found in Aloe Vera gel must be separated from the final extract because they are very irritating to the gut. An aloe product must be very soothing to the gut to promote healing.

Synergism is a property that many of the large Aloe companies tout who do not have the patented technology to extract stabilized mucilaginous polysaccharides. In other words, many of these companies claim that all 100 of the various ingredients found in Aloe Vera must be present for healing to occur. None of these claims have any basis in scientific research, while there is an abundance of research to prove that the mucilaginous polysaccharide is the sole ingredient responsible for all the healing properties attributed to Aloe.


Research by the immunologist Ian Tizard, PhD and virologist Maurice Kemp, PhD from Texas A&M led to the discovery that Aloe mucilaginous polysaccharide is taken into a special leukocyte, the macrophage, and this cell is stimulated to release messenger molecules called cytokines (interferons, interleukines, prostaglandins, tumor necrosis factor and stem cell growth factors. )

Tumors release a chemical that attracts blood circulation so that malignant cells have a supply of nutrition and can keep multiplying. Tumor necrosis factor shuts off the blood supply to the tumor and therefor it dies. All of the immune modulating effects from Aloe contribute greatly to the prevention and healing of malignant cells.

Danhof's Albarin is being shown to successfully treat about 80% of all cancer patients at The Medical Center for Preventative and Nutritional Medicine, and it is criminal that the FDA has seized the Albarin.

(How likely is the FDA to grant an IND given this raid? Typically, the FDA will grant an IND if one in 50 patients respond favorably to a new treatment. DiStefano has had an 80% success rate with Albarin, and it is apparent that many mainstream oncologists fear it as unwanted economic competition- the complete Albarin treatment has only cost patients $1100., regardless of how many treatments may be needed. Thats less than a typical charge for a week's worth of chemotherapy.)

Joe DiStefano started with the Albarin by successfully treating his own cancer. The first lOO patients he used it on all came from Hospice where they had been told they only had 2-3 months to live, and Joe only lost 6 out of 100 of them.




Paul Schebell, 48, from Connecticut, Advanced Metastatic Prostate/Liver Cancer. Had onset in '98, was diagnosed by PSA levels and bonescan. Despite Lupron and hormone shots, the cancer kept progressing. Learning of the Albarin clinics through a chance phone call with a friend, he started on Albarin in July of 2001. Having been told death was imminent, he now feels much stronger mentally and physically. He can now walk much easier and can concentrate well enough to read. The only side effects from the Albarin are chills. He was stunned by the FDA raid saying "It would be almost ludicrous if not so tragic." He said that his chances will be "greatly diminished" if he can't get Albarin. When the FDA raided, he was receiving treatment and the FDA asked everyone if they wanted to stop. Not one hand went up, they all wanted to keep receiving treatment. Schebell was outraged and told them. "We're all adults here making free will choices."

Along with all the other people interviewed, Schebell stated that there had been no charge for the initial consultation, that the full Albarin treatment only cost $1100. No matter how many treatments were necessary. (He along with all patients stated that their mainstream treatment costs had been into the tens of thousands of dollars, some into the hundreds of thousands.) He (along with all patients) stated that at no time did Joe DiStefano ever hold himself out to be a doctor, they knew him to be a licensed nutrition counselor and they all stated that Daniel Mayer, DO was always present to advise them on their treatments. Schebell could be dead within a month unless he can keep getting his Albarin.


Peggy Marsh, 54 from Tampa Florida was diagnosed with Breast Cancer in '94. Diagnosis was made by biopsy, ultrasound, mammogram. She had a radical mastectomy, radiation, and chemo therapy through the Moffit Cancer Center in Tampa. She had 5 lymph nodes become cancerous by the time they did the open biopsy. After every chemo treatment she lay in bed for 5 days unable to move. They made her sick as a dog, very nauseated. The radiation caused multiple infections forcing her to constantly return to the hospital.

She had a grapefruit sized tumor in her liver a year and a half ago and was only given 6 months to live. She credits the Albarin with helping her to beat these odds. She was treated at the bone marrow clinic at Moffit Cancer Center in Tampa by Dr.Karen Fields, who ultimately issued an ultimatum- that she "had to trust" her medical expertise, and that she could only do either the albarin or chemo, but not both, even though Peggy wanted to keep using both and felt that both were vitally necessary in her case. Marsh, who was trained as a nutritionist and is a Cornell graduate, feels that this is an economic control issue, noting that "All of my Albarin treatments cost me only what one week of chemo costs now." She feels strongly that Moffit might be part of the complaint against Albarin to the FDA, and if that's the case, then Field's violated her trust. "I shared with her about the Albarin study, and if she initiated the complaint to the FDA, she is now jeopardizing not only my life, but the lives of all the patients taking Albarin." Marsh could be dead within a month if she can't keep getting her Albarin.


Will Weinand, 54 from Chicago, started Albarin treatment in March of this year due to cancer in his prostate, spine, and hips. He had his prostate removed, but a year later discovered his cancer had spread to his spine and hips. He did hormone therapy and had severe pain in his lower spine at the T -4 and T -5 vertebrae The pain was so bad from this he had trouble getting out of bed and showering. Mainstream doctors told him he should have 21 days of radiation, and that he wouldn't live longer than a year. They told him the best they could do was pain management. After 6 weeks on the Albarin, the pain began to subside and was gone completely in 3 months. A recent MRI showed that the tumor between T -4 and T -5 vertebrae were gone, as well as the tumor in his left hip, but he still has cancer in his right hip and sacrum according to medical testing. He is very worried that the cancer will start spreading again without the Albarin, and is very disappointed that the government is strong arming their way in, stopping his Albarin treatment when it was clearly working. Will could be dead within a month if he can't resume his Albarin treatment.


Pari Thiern, 58 from Tampa FL had her thyroid removed due to cancer but still has lung and lymph node cancer which metastasized to the bone. She had a huge tumor on the left side of her neck that was going to choke her. After having her thyroid removed at McDill Airforce Base, they wanted to also remove the tumor in her neck and give her chemo and radiation. She refused having watched her first husband die from chemo and radiation, electing to try the Albarin after learning of the clinic at a local health food store via her son. Terrified that she could not afford the Albarin treatment, she was put at ease by Joe and Dr.Mayer who told her not to worry about the $1100. Cost, but to just begin her treatment which she did.

When she first started treatment she could not talk due to the tumor in her neck. She'd made four visits to the emergency room due to chronic infections which no antibiotics helped and was always sick with colds. The only side effects from the Albarin was coldness that went away shortly after each treatment. A catscan indicates that she is now free of cancer, and she is doing 100% better. She is terrified that her cancer will now return and pleads for the return of her Albarin saying "I can't believe this is happening in America."Greatly angered that her medical records were seized in the raid, she is now pleading for the President, her Senators and Congressmen to go to McDi11 Airforce base to look at her records and to see for himself how sick she was.


Robert Becks, 58 year old roofer from Clearwater, FL had a softball sized tumor in his neck which started growing 4 years ago and got enlarged a year and a half ago. It was diagnosed by cat scan, xrays and blood tests. It was too late for surgery, which would have been disfiguring. Holding the view that chemicals and radiation CAUSE cancer, it didn't make much sense to him to have mainstream treatments, which he refused. On December 12, 2000 he began Albarin treatment having learned of it by word of mouth. He was told the cost was $1100. which he could only partially afford to pay. He said Joe was "absolutely wonderful" about not pressing him financially and that he still owed the balance of his payment calling DiStefano and Mayer "The good guys with white hats."

Becks had 70 treatments, 4 per week and the Albarin "stopped the tumor right in its tracks". He said that for awhile he was too sick to resume treatments, and during that time the tumor started growing again, but went away again after treatment was resumed. He was able to stop taking morphine for pain due to the Albarin. Along with all the others interviewed, Becks stated that at no time did DiSteffano ever claim to be a doctor, but that he often called him "Doctor Joe" out of respect and appreciation. Along with all the others he stated that Dr.Mayer had always been present to consult on his treatment. Becks stated with regards to the raid. "This is crazy! I need my Albarin! I personally will do everything possible to get it back! The government has issued me a death sentence! Go look at the statistics, even the head of the Moffit Cancer Center did not take his own treatments when he got cancer, he used alternative treatment!"


Miles Cooper from Shelby NC is a gospel singer who has sung in the Grand Ole Opry in Nashville. He had stage 4 prostate cancer with enlarged lymph nodes and his prostate was pushed against his bladder. His PSA was 187 and he was told he had 6 months to a year to live. He learned of the Albarin treatment by word of mouth while discussing his cancer with friends at church and began treatment in April 2001. He had 86 treatments with Albarin and his PSA went from 187 to 0. 9 in 30 days. An MRI showed normal lymph nodes, and that his Prostate was beginning to shrink. Three weeks ago his PSA was 0.19, and his prostate was still shrinking. He is very concerned that without the Albarin his cancer, which is now in remission, will come back Miles is working very hard to help organize his fellow patients, as are several others. His quiet Christian faith is standing in good stead. He sincerely hopes that the courts and Congress will intercede to help get Albarin back, and that everyone reading this will help as well.


It is essential that everyone call their Senators and Congressmen to request an immediate oversight hearing of the FDA to force them to give the Albarin back to Joseph DiStefano and Dr.Mayer so that these patients can resume treatment. You can reach any member of congress via the Capital Switchboard at 202-225-3121. Especially be sure to call Congressman Dan Burton, Chair of the House Government Reform Committee. He had held other hearings to reign in the FDA and he must hold one very quickly to address this matter.

People living in St.Petersburg and Tampa should specifically call Rep Bill Young at 727-893-3191, and Rep Jim Davis at 813-354-9217 Tell them both that people have a right to freedom of choice in healthcare.

Post this on websites, and forward it to everyone you know- several people's lives are in direct jeopardy, and we must work together to help them get their Albarin back.

Forward this to radio and TV talk show hosts who can air this story If you can get Joe DiStefano onto any large radio or TV shows, contact him via The Medical Center for Preventive and Nutritional Medicine Inc.727-344-3134, 813-968-5998.

Badly needed donations for the legal fund for the Medical Center for Preventive and Nutritional Medicine can be made to:

Joe DiStefano Legal Defense Fund
c/o 6701-C 38th Ave. N.
St.Petersburg, FL 33710



Dendritic Cell Therapy


DC Therapy

What is DC Therapy?


Dendritic Cell (DC) Therapy or so-called Dendritic Cell vaccine is a newly emerging and potent form of immune therapy used to treat cancer. Only recently (2010) approved by the US FDA, dendritic cell therapy is an immune therapy which harnesses the body’s own immune system to fight cancer. The dendritic cell itself is an immune cell whose role is the recognition, processing and presentation of foreign antigens to the T-cells in the effector arm of the immune system. Although dendritic cell are potent cells, they are not usually present in adequate quantity to allow for a potent immune response. Dendritic cell therapy thus involves the harvesting of blood cells (monocytes) from a patient and processing them in the laboratory to produce dendritic cells which are then given back to a patient in order to allow massive dendritic cell participation in optimally activating the immune system. To learn more about vaccine and dendritic cell therapy for cancer, please read the following articles:

The National Cancer Institute has a very concise primer on Treating and Preventing Cancer with Vaccines on their site.

Dendritic cells and immunity against cancer” by K. Palucka, H. Ueno1, J. Fay, and J. Banchereau of Baylor Institute for Immunology Research and Sammons Cancer Center, Baylor University Medical Center,Dallas, TX; and Department of Gene and Cell Medicine and Department of Medicine, Immunology Institute, Mount SinaiSchool ofMedicine, New York,NY,USA as published in Journal of Internal Medicine.

Volume 269, Issue 1, 2010.

Dendritic Cells (I): Biological functions” and “Dendritic Cells (II) Role and therapeutic implications in cancer” by S. Satthaporn and O. Eremin of the U. of Nottingham and Lincoln County Hospital, UK as published in J. of the Royal College Surgeons, Edinb.
46:9-20 and 159-167, 2001.

Clinical Applications of Dendritic Cell Cancer Vaccines” by Dr. Joseph Barr of the U. of Pittsburgh Cancer Institute, Pittsburgh, PA USA in The Oncologist 4(2): 140-144, 1999.

Also, a slide show / lecture presentation by Dr. Michael Morse on “Current Status of Dendritic-Cell Vaccines” is available on the Medscape site from WebMD as part of an educational session on “Therapeutic Cancer Vaccines: Targeting the Future of Cancer Treatment” but requires registration to enter the site.

There is also a youtube video presentation on “Using Dendritic Cells to Create Cancer Vaccines” by Professor Edgar Engleman of Standford University.

Abstracts of recent reviews on Pubmed include articles by IG Schmidt-Wolf et al. on “Dendritic Cell, the immunotherapeutic cell for cancer”, TL Whiteside and C Odous from U. of Pittsburgh Cancer Institute on “Dendritic cell biology and cancer therapy”, EM Hersh et al. on “Clinical Applications of dendritic cell vaccination in the treatment of cancer

Also, please refer to our Research Archives for many related abstracts on the therapy.


Therapeutic intervention: 

GcMAF-The cancer revolution from Japan



GcMAF - treatment for cancer, aids and immune diseases

It is our immune system that prevents and cures cancer

A macrophage (purple) eats cancer cellsA macrophage (purple) eats cancer cells

The first research was published in 1993 and since then many papers have appeared indicating GcMAF cured Cancer and eradicated HIV by simply activating the immune system.

Dr. Nobuto Yamamoto in Philadelphia was the first, but hundreds of scientists have now worked on this and related projects.

How does GcMAF work?
In a healthy person GcMAF instructs macrophages in our bloodstream to scour our bodies and kill malignancies. But malignant cells like cancer send out an enzyme called Nagalase that neutralises the GcMAF; so the macrophages never get the message to go into action – in this way cancer suppresses the immune system, and cancer cells grow unchecked.

To reverse this, we make GcMAF outside the body, and it is injected once a week for 25 weeks for early cancers, 50 or more weeks for late stage cancers. (Encapsulated tumours require additional treatment.) HIV can require as little as 16 weeks.

In its role of immune system regulator, GcMAF reverses other diseases that attack the immune system like Osteoporosis, Aids, Hodgkin’s, Lupus, MS, Fibromyalgia, Parkinson’s, various bacterial and viral infections and various types of Immune dysfunction.

Small pre-clinical trials to build the case are again taking place.

Our GcMAF destroying human cancer cells for 72 hours. At 100ng/ml, panel D, cells show an irregular shape and size. They are significantly smaller as if processes of shrinkage had occurred. Cells appear inhomogeneous and both cytoplasm and nucleus appear irregular as if fragmented. Numerous cellular debris can be observed as well as apoptotic bodies. Clusters are much fewer in number and their borders appear less defined.Our GcMAF destroying human cancer cells for 72 hours. At 100ng/ml, panel D, cells show an irregular shape and size. They are significantly smaller as if processes of shrinkage had occurred. Cells appear inhomogeneous and both cytoplasm and nucleus appear irregular as if fragmented. Numerous cellular debris can be observed as well as apoptotic bodies. Clusters are much fewer in number and their borders appear less defined.

Those diagnosed with any of these illnesses, and who have done their own research on it,  are invited to respond. We ask for a copy of diagnostic information and update reports from a physician during and after treatments, to help build the case that GcMAF is a cure for various illnesses, which will help to make it available to the public. Participants are free to stop at any time.

What have we learned?

Dr Yamamoto carefully selected his trials: he took fit people with in the early stages of cancer and HIV, and reported 100% success, with no recurrence after many years. He did not attempt to cure people with large tumours.

Our trials are quite different: most people are over 50, some over 70, with advanced or terminal cancers, with significant tumour mass.

We appear to have had stunning results in 20 percent of cases, and we think we have learned enough to take that figure up to 50% in this 2011 round of trials. GcMAF needs normal levels of vitamin D to function strongly, and those participants see significant tumour shrinkage in 8 weeks. But even in low responders, GcMAF appears to stop the advance of cancer.

We have probably proved GcMAF can work for people up to age 67, with terminal stage 4 cancer, and can completely destroy large tumour mass.

So far those patients who in 8 weeks are cured of symptoms, or whose tumour mass drops significantly, all take exercise, perhaps a 40 minute walk outside each day.

HIV participants should expect to see viral loads drop to zero, and CD4 counts rise by at least 300 points in 16 weeks, and if that doesn't happen we will refund your money.

But the beauty of using your own immune system to cure cancer is that it remembers how to defeat it for the rest of your life: it doesn't come back. And unlike chemotherapy, the side effects are trivial.

Therapeutic Substance(s): 

Low Dose naltrexone


Low Dose Naltrexone


LDN: Editor's Blog

Major International Progress — Oct 2016

Immune Therapeutics, Inc. has vigorous plans for its Lodonal brand of LDN‬

At its recent stockholders meeting, the company announced ‪its intention to seek approval of Lodonal by the United Nations, the President’s Emergency Plan for AIDS Relief, and UNAIDS. In addition, it is awaiting a meeting with the FDA to discuss plans for a trial of Lodonal for Crohn’s Disease.

Click here to learn more about plans for Africa and elsewhere...


FDA-approved naltrexone, in a low dose, can normalize the immune system — helping those with HIV/AIDS, cancer, autoimmune diseases, and central nervous system disorders.


Welcome to the Low Dose Naltrexone (LDN) Home Page


Updated: Oct 17, 2016

The authors of this website do not profit from the sale of low-dose naltrexone or from website traffic, and are in no way associated with any pharmaceutical manufacturer or pharmacy.

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For announcements and discussion about Low Dose Naltrexone,
subscribe to the LDN Yahoo Group:

The LDN Yahoo Group is an announcement and discussion group for those interested in LDN, and who wish to be notified about updates to this website. We expect that official announcements to the group will be fairly infrequent, typically not more than one per month. Group members not wishing to receive general discussion e-mail from other members may set their message delivery option to "Special Notices" when joining, or by logging on to the LDN Yahoo Group site and clicking on "Edit My Membership."



“Low Dose Naltrexone (LDN) may well be the most important therapeutic breakthrough in over fifty years. It provides a new, safe and inexpensive method of medical treatment by mobilizing the natural defenses of one’s own immune system.

“LDN substantially reduces health care costs and improves treatment of a wide array of diseases. Unfortunately, because naltrexone has been without patent protection for many years, no pharmaceutical company will bear the expense of the large clinical trials necessary for FDA approval of LDN’s new special uses. It is now up to public institutions to seize the opportunity that LDN offers.”

  — David Gluck, MD


LDN: The Latest Research

International Journal of Oncology — June 2016

LDN Possesses Anticancer Activity

Wai M. Liu, Katherine A. Scott, et al of the Department of Oncology, St. George's University of London, report that they evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and that “our data support further the idea that LDN possesses anticancer activity.”

Click here to learn more...


LDN Website Contents

> On this page you can find answers to these questions:

> You can go to more detailed information on these linked pages:



CBS News Reports:
"Wonder drug" LDN Could Help Treat Cancer, Multiple Sclerosis

JACKSONVILLE, FLA (CBS) — February, 2008 — This report features an interview with Lori Miles, an MS sufferer who can now walk again, thanks to LDN. Also quoted in the piece is Dr. Daniel Kantor, neurologist and director of the Comprehensive Multiple Sclerosis Program at the Shands Jacksonville Neuroscience Institute: "I would like all of us to write to our congressmen, ask the FDA and NIH—National Institutes of Health—to fund more research about LDN."


What is low-dose naltrexone and why is it important?

> Low-dose naltrexone holds great promise for the millions of people worldwide with autoimmune diseases or central nervous system disorders or who face a deadly cancer.

> In the developing world, LDN could provide the first low-cost, easy to administer, and side-effect-free therapy for HIV/AIDS.

Naltrexone itself was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs. By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that our brain and adrenal glands produce: beta-endorphin and metenkephalin. Many body tissues have receptors for these endorphins and enkephalins, including virtually every cell of the body's immune system.

In 1985, Bernard Bihari, MD, a physician with a clinical practice in New York City, discovered the effects of a much smaller dose of naltrexone (approximately 3mg once a day) on the body's immune system. He found that this low dose, taken at bedtime, was able to enhance a patient's response to infection by HIV, the virus that causes AIDS. [Note: Subsequently, the optimal adult dosage of LDN has been found to be 4.5mg.]

In the mid-1990's, Dr. Bihari found that patients in his practice with cancer (such as lymphoma or pancreatic cancer) could benefit, in some cases dramatically, from LDN. In addition, people who had an autoimmune disease (such as lupus) often showed prompt control of disease activity while taking LDN.


First Study of LDN Published
in US Medical Journal

Dr. Jill Smith’s original article, "Low-Dose Naltrexone Therapy Improves Active Crohn’s Disease," in the January issue of the American Journal of Gastroenterology (2007;102:1–9), officially presents LDN to the world of scientific medicine. Smith, Professor of Gastroenterology at Pennsylvania State University's College of Medicine, found that two-thirds of the patients in her pilot study went into remission and fully 89% of the group responded to treatment to some degree. She concluded that “LDN therapy appears effective and safe in subjects with active Crohn’s disease.” (For further information on Smith's study, please see the linked Clinical Trials page.)

Endoscopic Improvement in Crohn’s Colitis with Naltrexone
Figure A: Shown is the rectum of a subject with active Crohn’s Disease before starting therapy with naltrexone 4.5 mg/day. The mucosa is ulcerated, edematous, and inflamed.
Figure B: Shows the same area of the rectum in the same patient four weeks after naltrexone therapy. The lining is now healed, ulcers resolved, and the mucosa is healthy.
Copyrights: do not reproduce the above images and captions without written permission from Jill P. Smith, MD, Professor of Medicine, H-045 GI Division, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033


How does LDN work?

> LDN boosts the immune system, activating the body's own natural defenses.

Up to the present time, the question of "What controls the immune system?" has not been present in the curricula of medical colleges and the issue has not formed a part of the received wisdom of practicing physicians. Nonetheless, a body of research over the past two decades has pointed repeatedly to one's own endorphin secretions (our internal opioids) as playing the central role in the beneficial orchestration of the immune system, and recognition of the facts is growing.

Witness these statements from a review article of medical progress in the November 13, 2003 issue of the prestigious New England Journal of Medicine: "Opioid-Induced Immune Modulation: .... Preclinical evidence indicates overwhelmingly that opioids alter the development, differentiation, and function of immune cells, and that both innate and adaptive systems are affected.1,2 Bone marrow progenitor cells, macrophages, natural killer cells, immature thymocytes and T cells, and B cells are all involved. The relatively recent identification of opioid-related receptors on immune cells makes it even more likely that opioids have direct effects on the immune system.3"

The brief blockade of opioid receptors between 2 a.m. and 4 a.m. that is caused by taking LDN at bedtime each night is believed to produce a prolonged up-regulation of vital elements of the immune system by causing an increase in endorphin and enkephalin production. Normal volunteers who have taken LDN in this fashion have been found to have much higher levels of beta-endorphins circulating in their blood in the following days. Animal research by I. Zagon, PhD, and his colleagues has shown a marked increase in metenkephalin levels as well. [Note: Additional information for Dr. Zagon can be found at the end of this page.]

Bihari says that his patients with HIV/AIDS who regularly took LDN before the availability of HAART were generally spared any deterioration of their important helper T cells (CD4+).

In human cancer, research by Zagon over many years has demonstrated inhibition of a number of different human tumors in laboratory studies by using endorphins and low dose naltrexone. It is suggested that the increased endorphin and enkephalin levels, induced by LDN, work directly on the tumors' opioid receptors — and, perhaps, induce cancer cell death (apoptosis). In addition, it is believed that they act to increase natural killer cells and other healthy immune defenses against cancer.

In general, in people with diseases that are partially or largely triggered by a deficiency of endorphins (including cancer and autoimmune diseases), or are accelerated by a deficiency of endorphins (such as HIV/AIDS), restoration of the body's normal production of endorphins is the major therapeutic action of LDN.


ABC News Reports:
LDN a "Wonder Drug?"

By Ali Gorman

Hershey, Pa. - May 21, 2008 (WPVI) -- It's a drug already helping thousands of people battle addiction, but many people believe it also has the potential to help tens-of-thousands of patients with diseases like Crohn's, multiple sclerosis, Lupus, Parkinson's and even HIV.

It's called low dose naltrexone or LDN. Many patients who've tried it said it works and doesn't have bad side effects. But getting it to a pharmacy near you could be difficult. [Please click to read more. Video no longer available.]


What diseases has it been useful for and how effective is it?

> Bernard Bihari, MD, as well as other physicians and researchers, have described beneficial effects of LDN on a variety of diseases:

  • Bladder Cancer
  • Breast Cancer
  • Carcinoid
  • Colon & Rectal Cancer
  • Glioblastoma
  • Liver Cancer
  • Lung Cancer (Non-Small Cell)
  • Lymphocytic Leukemia (chronic)
  • Lymphoma (Hodgkin's and Non-Hodgkin's)
  • Malignant Melanoma
  • Multiple Myeloma
  • Neuroblastoma
  • Ovarian Cancer
  • Pancreatic Cancer
  • Prostate Cancer (untreated)
  • Renal Cell Carcinoma
  • Throat Cancer
  • Uterine Cancer
Other Diseases
  • Common Colds (URI’s)
  • Emphysema (COPD)
  • Depression (Major; and Bipolar)
  • Lyme Disease (LATE Stage)

  • ALS (Lou Gehrig's Disease)
  • Alzheimer's Disease
  • Autism Spectrum Disorders
  • Hereditary Spastic Paraparesis
  • Multiple Sclerosis (MS)
  • Parkinson's Disease
  • Post-Polio Syndrome
  • Post-Traumatic Stress Disorder (PTSD) 
  • Primary Lateral Sclerosis (PLS)
  • Progressive Supranuclear Palsy
  • Transverse Myelitis

Other Autoimmune Diseases:
  • Ankylosing Spondylitis
  • Behcet's Disease
  • Celiac Disease
  • Chronic Fatigue Syndrome
  • CREST syndrome
  • Crohn's Disease
  • Dermatomyositis
  • Dystonia
  • Endometriosis
  • Fibromyalgia
  • Hashimoto’s Thyroiditis
  • Irritable Bowel Syndrome (IBS)
  • Myasthenia Gravis (MG)
  • Nephrotic Syndrome
  • Pemphigoid
  • Primary Biliary Cirrhosis
  • Psoriasis
  • Rheumatoid Arthritis
  • Sarcoidosis
  • Scleroderma
  • Sjogren’s Syndrome
  • Stiff Person Syndrome (SPS)
  • Systemic Lupus (SLE)
  • Ulcerative Colitis
  • Wegener's Granulomatosis

> LDN has demonstrated efficacy in thousands of cases.

Cancer. As of mid-2004, Dr. Bihari reported having treated over 300 patients who had a cancer that had failed to respond to standard treatments. Of that group, some 50%, after four to six months treatment with LDN, began to demonstrate a halt in cancer growth and, of those, over one-third have shown objective signs of tumor shrinkage.

Autoimmune diseases. Within the group of patients who presented with an autoimmune disease (see above list), none have failed to respond to LDN; all have experienced a halt in progression of their illness. In many patients there was a marked remission in signs and symptoms of the disease. The greatest number of patients within the autoimmune group are people with multiple sclerosis, of whom there were some 400 in Dr. Bihari's practice. Less than 1% of these patients has ever experienced a fresh attack of MS while they maintained their regular LDN nightly therapy.

HIV/AIDS. As of September 2003, Dr. Bihari had been treating 350 AIDS patients using LDN in conjunction with accepted AIDS therapies. Over the prior 7 years over 85% of these patients showed no detectable levels of the HIV virus — a much higher success rate than most current AIDS treatments, and with no significant side effects. It is also worth noting that many HIV/AIDS patients have been living symptom-free for years taking only LDN with no other medications.

Central Nervous System disorders. Anecdotal reports continue to be received concerning beneficial effects of LDN on the course of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS—Lou Gehrig’s disease), and primary lateral sclerosis. Dr. Jaquelyn McCandless has found a very positive effect of LDN, in appropriately reduced dosage and applied as a transdermal cream, in children with autism.

> How is it possible that one medication can impact such a wide range of disorders?

The disorders listed above all share a particular feature: in all of them, the immune system plays a central role. Low blood levels of endorphins are generally present, contributing to the disease-associated immune deficiencies.

Research by others — on neuropeptide receptors expressed by various human tumors — has found opioid receptors in many types of cancer:

  • Brain tumors (both astrocytoma and glioblastoma)
  • Breast cancer
  • Endometrial cancer
  • Head and neck squamous cell carcinoma
  • Myeloid leukemia
  • Lung cancer (both small cell and non-small cell)
  • Neuroblastoma and others...

These findings suggest the possibility for a beneficial LDN effect in a wide variety of common cancers.

How can I obtain LDN and what will it cost?

> LDN can be prescribed by your doctor, and should be prepared by a reliable compounding pharmacy.

Naltrexone is a prescription drug, so your physician would have to give you a prescription after deciding that LDN appears appropriate for you.

Naltrexone in the large 50mg size, originally manufactured by DuPont under the brand name ReVia, is now sold by Mallinckrodt as Depade and by Barr Laboratories under the generic name naltrexone.

LDN prescriptions are now being filled by hundreds of local pharmacies, as well as by some mail-order pharmacies, around the US. Some pharmacists have been grinding up the 50mg tablets of naltrexone to prepare the 4.5mg capsules of LDN; others use naltrexone, purchased as a pure powder, from a primary manufacturer.

> LDN is not expensive.

One of the first pharmacies to compound LDN was Irmat Pharmacy in Manhattan. Their current price for a one month supply (30 capsules) of LDN is $45 dollars (for 4.0mg and greater; $37.50 for less than 4.0mg). Irmat does monthly quality control testing on its LDN, and will accept prescriptions from any licensed practitioner. No insurance is accepted. It can ship to the majority of states in the United States, but not internationally.

> Pharmacies that are known to be reliable compounders of LDN:

Irmat Pharmacy, New York, NY (212) 685-0502 (212) 532-6596
Belmar Pharmacy, Lakewood, CO (800) 525-9473 (866) 415-2923
The Compounder Pharmacy, Aurora, IL (630) 859-0333
(800) 679-4667
(630) 859-0114
The Pharmacy Shop and
Compounding Center, Canandaigua, NY
(585) 396-9970
(800) 396-9970
(585) 396-7264
McGuff Compounding Pharmacy,
Santa Ana, CA
(714) 438-0536
(877) 444-1133
(877) 444-1155
Skip's Pharmacy, Boca Raton, FL (561) 218-0111
(800) 553-7429
(561) 218-8873
The Medicine Store Pharmacy, Concord, NH (603) 225-2747
(877) 926-7637
(603) 224-3661
Smith's Pharmacy, Toronto, Canada (416) 488-2600
(800) 361-6624
(416) 484-8855
Dickson Chemist, Glasgow, Scotland +44-141-647-8032


IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release form.

Reports have been received from patients that their pharmacies have been supplying a slow-release form of naltrexone. Pharmacies should be instructed NOT to provide LDN in an "SR" or slow-release or timed-release form. Unless the low dose of naltrexone is in an unaltered form, which permits it to reach a prompt "spike" in the blood stream, its therapeutic effects may be inhibited.

Fillers. Capsules of LDN necessarily contain a substantial percentage of neutral inactive filler. Experiments by the compounding pharmacist, Dr. Skip Lenz, have demonstrated that the use of calcium carbonate as a filler will interfere with absorption of the LDN capsule. Therefore, it is suggested that calcium carbonate filler not be employed in compounding LDN capsules. He recommends either Avicel, lactose (if lactose intolerance is not a problem), or sucrose fillers as useful fast-release fillers.

> IMPORTANT: Make sure to fill your Rx at a compounding pharmacy that has a reputation for consistent reliability in the quality of the LDN it delivers.

The FDA has found a significant error rate in compounded prescriptions produced at randomly selected pharmacies. Dr. Bihari has reported seeing adverse effects from this problem. Please see our report, Reliability Problem With Compounding Pharmacies. Please see the above list of recommended pharmacies for some suggested sources.

What dosage and frequency should my physician prescribe?

The usual adult dosage is 4.5mg taken once daily at night. Because of the rhythms of the body's production of master hormones, LDN is best taken between 9pm and 3am. Most patients take it at bedtime.

Notable exceptions:

  • People who have multiple sclerosis that has led to muscle spasms are advised to use only 3mg daily and to maintain that dosage.
  • For intial dosage of LDN in those patients who have Hashimoto’s thyroiditis with hypothyroidism and who are taking thyroid hormone replacement medication, please read Cautionary Warnings, below.

Rarely, the naltrexone may need to be purchased as a solution — in distilled water — with 1mg per ml dispensed with a 5ml medicine dropper. If LDN is used in a liquid form, it is important to keep it refrigerated.

The therapeutic dosage range for LDN is from 1.5mg to 4.5mg every night. Dosages below this range are likely to have no effect at all, and dosages above this range are likely to block endorphins for too long a period of time and interfere with its effectiveness.

> IMPORTANT: Make sure to specify that you do NOT want LDN in a slow-release form (see above).

Are there any side effects or cautionary warnings?

> Side effects:

LDN has virtually no side effects. Occasionally, during the first week's use of LDN, patients may complain of some difficulty sleeping. This rarely persists after the first week. Should it do so, dosage can be reduced from 4.5mg to 3mg nightly.

> Cautionary warnings:

  1. Because LDN blocks opioid receptors throughout the body for three or four hours, people using medicine that is an opioid agonist, i.e. narcotic medication — such as Ultram (tramadol), morphine, dextromethorphan, Percocet, Duragesic patch or codeine-containing medication — should not take LDN until such medicine is completely out of one's system. Patients who have become dependant on daily use of narcotic-containing pain medication may require 10 days to 2 weeks of slowly weaning off of such drugs entirely (while first substituting full doses of non-narcotic pain medications) before being able to begin LDN safely.
  2. Those patients who are taking thyroid hormone replacement for a diagnosis of Hashimoto’s thyroiditis with hypothyroidism ought to begin LDN at the lowest range (1.5mg for an adult). Be aware that LDN may lead to a prompt decrease in the autoimmune disorder, which then may require a rapid reduction in the dose of thyroid hormone replacement in order to avoid symptoms of hyperthyroidism.
  3. Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.
  4. People who have received organ transplants and who therefore are taking immunosuppressive medication on a permanent basis are cautioned against the use of LDN because it may act to counter the effect of those medications.

When will the low-dose use of naltrexone become FDA approved?

> Although naltrexone itself is an FDA-approved drug, the varied uses of LDN still await application to the FDA after related scientific clinical trials.

The FDA approved naltrexone at the 50mg dosage in 1984. LDN (in the 3mg or 4.5mg dosage) has not yet been submitted for approval because the prospective clinical trials that are required for FDA approval need to be funded at the cost of many millions of dollars.

The successful results of the first US medical center research on LDN, an open-label trial that tested the use of LDN in Crohn’s disease (details here), was presented in May 2006 by Professor Jill Smith of the Pennsylvania State University College of Medicine. The National Institutes of Health has granted $500,000 for Dr. Smith's group to continue the study as a larger placebo-controlled scientific trial of LDN in Crohn's disease.

All physicians understand that appropriate off-label use of an already FDA-approved medication such as naltrexone is perfectly ethical and legal. Because naltrexone itself has already passed animal toxicity studies, one could expect that once testing is able to begin, LDN could complete its clinical trials in humans and receive FDA approval for one or more uses within two to four years.

What You Can Do

> Talk to your doctor.

If you are suffering from HIV/AIDS, cancer, or an autoimmune disease, LDN could help. In AIDS and cancer therapy, LDN is often used in conjunction with other medications.

Cancer. Anyone with cancer or a pre-cancerous condition should consider LDN. Many use LDN as a preventive treatment. Post-treatment, others have been using LDN to prevent a recurrence of their cancer. LDN has been shown in many cases to work with virtually incurable cancers such as neuroblastoma, multiple myeloma, and pancreatic cancer.

HIV/AIDS. As an AIDS drug, LDN leads to far fewer side effects than the standard "AIDS cocktail." When used in conjunction with HAART therapies, LDN can boost T-cell populations, prevent disfiguring lipodystrophy, and lower rates of treatment failure.

Do not be afraid to approach your doctors — physicians today are increasingly open to learning about new therapies in development. Tell your doctors about this website, or print out and hand them the information, and let them weigh the evidence.

> Tell others.

If someone you know has HIV/AIDS, cancer, an autoimmune disease, or one of the aforementioned central nervous system disorders, LDN could save them from a great deal of suffering. If they use e-mail, send them the address of this website ( Or, print out the site and mail them the information.

> Help spread the word to the media, the medical community, and to developing countries.

Low-dose naltrexone has the potential to reduce the terrible human loss now taking place throughout the globe. It is a drug that could prevent millions of children from becoming AIDS orphans. It is a drug that could be a powerful ally in the war against cancer.

If you or someone you know has connections in the media, the medical community, or to those in developing countries involved in AIDS policy or treatment, please let them know about LDN.

About This Website

> This is a not-for-profit website.

This website is sponsored by Advocates For Therapeutic Immunology. The purpose of this website is to provide information to patients and physicians about important therapeutic breakthroughs in advanced medical immunology. The authors of this site do not profit from the sale of low-dose naltrexone or from website traffic, and are in no way associated with any pharmaceutical manufacturer or pharmacy.

> Consult your doctor.

This website is not intended as a substitute for professional medical help or advice. A physician should always be consulted for any medical condition.

> Contact us.

For information on how to contact us with questions or comments, click here.

Please note that no response can be given to individual questions concerning medical symptoms or treatment.

Additional Information

  • Bernard Bihari, MD, was the discoverer of the major clinical effects of low dose naltrexone. A private practitioner in Manhattan, Dr. Bihari was a Board-certified specialist in Psychiatry and Neurology. Dr. Bihari's curriculum vitae.
  • David Gluck, MD (NY Lic. #083512), is the editor of this website, He is a Board-certified specialist in both Internal Medicine and Preventive Medicine. Dr. Gluck has served as medical director for JCPenney and MetLife, and is now semi-retired, living and working in New York City. [Ed. Note: Please do not confuse David Gluck, MD with an unrelated doctor of similar name in New York, David A. Gluck, who is a specialist in Obstetrics and Gynecology.]
  • Ian S. Zagon, PhD, has spent over two decades in doing basic research concerning endorphins. He is Professor of Neural and Behavioral Sciences, Pennsylvania State University, Dept. of Neural and Behavioral Sciences, H-109, Hershey Medical Center, Hershey, PA 17033; office phone: (717) 531-6409; email:; website.


  1. Roy S, Loh HH. Effects of opioids on the immune system. Neurochem Res 1996;21:1375-1386
  2. Risdahl JM, Khanna KV, Peterson PK, Molitor TW. Opiates and infection. J Neuroimmunol 1998;83:4-18
  3. Makman MH. Morphine receptors in immunocytes and neurons. Adv Neuroimmunol 1994;4:69-82
Therapeutic Substance(s): 
Therapeutic intervention: 

Oncolytic Virus Treatment


From Wikipeda:

Oncolytic virus Treatment

From Wikipedia, the free encyclopedia

An oncolytic virus is a virus that preferentially infects and kills cancer cells.[1][2] As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour.[3][4] Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune responses.[5][6]

The potential of viruses as anti-cancer agents was first realised in the early twentieth century, although coordinated research efforts did not begin until the 1960s.[7] A number of viruses including adenovirus, reovirus, measles, herpes simplex, Newcastle disease virus and vaccinia have now been clinically tested as oncolytic agents.[8] Most current oncolytic viruses are engineered for tumour selectivity, although there are naturally occurring examples such as reovirus and the senecavirus,[9] resulting in clinical trials.[10]

The first oncolytic virus approved by a national regulatory agency is genetically not modified ECHO-7 strain enterovirus RIGVIR, approved in Latvia in 2004 for treatment of skin melanoma.[11] Later (in 2015 and 2016 respectively) it was also approved in Georgia (country)[12] and Armenia. In 2005 Chinese company, Shanghai Sunway Biotech registered an oncolytic adenovirus, a genetically modified adenovirus named H101. It gained regulatory approval in 2005 from the CFDA, for the treatment of head and neck cancer.[13] The drug talimogene laherparepvec (OncoVex, T-VEC) was the first oncolytic herpes virus ( a modified herpes simplex virus), approved for use by the USFDA and by the EMA in the EU in 2015 for the treatment of advanced inoperable melanoma. In a combined decision, members of the FDA's Oncology Drug Advisory Committee and Cellular, Tissue and Gene Therapies Advisory Committee voted 22-1 to recommend approval of the oncolytic immunotherapy.[14]



A connection between cancer regression and viruses has long been theorised, and case reports of regression noted in cervical cancer, Burkitt lymphoma and Hodgkin lymphoma, after immunisation or infection with an unrelated virus appeared at the beginning of the 20th century.[15] Efforts to treat cancer through immunisation or virotherapy (deliberate infection with a virus), began in the mid-20th century.[15][16] As the technology for creating a custom virus did not exist, all early efforts focused on finding natural oncolytic viruses. During the 1960s, promising research involved using poliovirus,[17] adenovirus,[15] Coxsackie virus,[18] ECHO enterovirus RIGVIR[19] and others.[16] The early complications were occasional cases of uncontrolled infection, resulting in significant morbidity and mortality; the very frequent development of an immune response, while harmless to the patient,[15] destroyed the virus and thus prevented it from destroying the cancer.[17] Only certain cancers could be treated through virotherapy was also recognised very early.[18] Even when a response was seen, these responses were neither complete nor durable.[15] The field of virotherapy was nearly abandoned for a time, as the technology required to modify viruses didn't exist and chemotherapy and radiotherapy technology enjoyed early success. However, now these technologies have been thoroughly developed, cancer is still a major cause of mortality and there is still a need for novel cancer therapies, this sidelined therapy has now gained renewed interest.[15][20]

Herpes simplex virus

Herpes simplex virus (HSV) was one of the first viruses to be adapted to attack cancer cells selectively, because it was well understood, easy to manipulate and relatively harmless in its natural state (merely causing cold sores) so likely to pose fewer risks. The herpes simplex virus type 1 (HSV-1) mutant 1716 lacks both copies of the ICP34.5 gene, and as a result is no longer able to replicate in terminally differentiated and non-dividing cells but will infect and cause lysis very efficiently in cancer cells, and this has proved to be an effective tumour-targeting strategy.[21][22] In a wide range of in vivo cancer models, the HSV1716 virus has induced tumour regression and increased survival times.[23][24][25]

In 1996, the first approval was given in Europe for a clinical trial using the oncolytic virus HSV1716. From 1997 to 2003, strain HSV1716 was injected into tumours of patients with glioblastoma multiforme, a highly malignant brain tumour, with no evidence of toxicity or side effects, and some long-term survivors.[26][27][28] Other safety trials have used HSV1716 to treat patients with melanoma and squamous-cell carcinoma of head and neck.[29][30] Since then other studies have shown that the outer coating of HSV1716 variants can be targeted to specific types of cancer cells,[31] and can be used to deliver a variety of additional genes into cancer cells, such as genes to split a harmless prodrug inside cancer cells to release toxic chemotherapy,[32] or genes which command infected cancer cells to concentrate protein tagged with radioactive iodine, so that individual cancer cells are killed by micro-dose radiation as well as by virus-induced cell lysis.[33]

Other oncolytic viruses based on HSV have also been developed and are in clinical trials, most notably OncoVex GM-CSF, developed by Amgen, which has successfully completed a pivotal Phase III trial for advanced melanoma. This study met its primary endpoint (durable response rate) with a very high degree of statistical significance in March 2013, the first positive phase 3 study for an oncolytic virus in the western world.[citation needed]

Oncorine (H101)

The first oncolytic virus to be approved by a regulatory agency was a genetically modified adenovirus named H101 by Shanghai Sunway Biotech. It gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer.[13][34] Sunway's H101 and the very similar Onyx-15 have been engineered to remove a viral defense mechanism that interacts with a normal human gene p53, which is very frequently dysregulated in cancer cells.[34] Despite the promises of early in vivo lab work, these viruses do not specifically infect cancer cells, but they still kill cancer cells preferentially.[34] While overall survival rates are not known, short-term response rates are approximately doubled for H101 plus chemotherapy when compared to chemotherapy alone.[34] It appears to work best when injected directly into a tumour, and when any resulting fever is not suppressed.[34] Systemic therapy (such as through infusion through an intravenous line) is desirable for treating metastatic disease.[35] It is now marketed under the brand name Oncorine.[36]

Mechanisms of action

Direct oncolysis

Direct oncolysis, the cell killing effect produced by viral infection of cancer cells, was the original concept of oncolytic viruses.[1][37] By specific infection of a tumour cell, the virus multiplies within it until it causes cell lysis, releasing a second generation of virus to then infect surrounding cells.[3]


With advances in cancer immunotherapy such as immune checkpoint inhibitors, increased interest was given to the prospect of oncolytic viruses as immunotherapies. There are two main considerations of the interaction between oncolytic viruses and the immune system.

Immunity as an obstacle

A major obstacle to the success of oncolytic viruses is the patient immune system which naturally attempts to deactivate any virus. This can be a particular problem for intravenous injection, where the virus must first survive interactions with the blood complement and neutralising antibodies.[38] It has been shown that immunosuppression by chemotherapy and inhibition of the complement system can enhance oncolytic virus therapy.[39][40][41]

Pre-existing immunity can be partly avoided by using viruses that are not common human pathogens. However, this does not avoid subsequent antibody generation. However, some studies have shown that pre-immunity to oncolytic viruses doesn't cause a significant reduction in efficacy.[42]

Alternatively, the viral vector can be coated with a polymer such as polyethylene glycol, shielding it from antibodies, but this also prevents viral coat proteins adhering to host cells.[43]

Another way to help oncolytic viruses reach cancer growths after intravenous injection, is to hide them inside macrophages (a type of white blood cell). Macrophages automatically migrate to areas of tissue destruction, especially where oxygen levels are low, characteristic of cancer growths, and have been used successfully to deliver oncolytic viruses to prostate cancer in animals.[44]

Immunity as an ally

Although it poses a hurdle by inactivating viruses, the patient's immune system can also act as an ally against tumors; infection attracts the attention of the immune system to the tumour and may help to generate useful and long-lasting antitumor immunity.[45][46] This essentially produces a personalised Cancer vaccine.

Many cases of spontaneous remission of cancer have been recorded, though not fully understood, they are thought likely to be a result of a sudden immune response or infection.[47] Efforts to induce this phenomenon have used cancer vaccines (derived from cancer cells or selected cancer antigens), or direct treatment with immune-stimulating factors on skin cancers.[48] Some oncolytic viruses are very immunogenic and may by infection of the tumour, elicit an anti-tumor immune response, especially viruses delivering cytokines or other immune stimulating factors.[49]

Oncolytic behaviour of wild-type viruses

Vesicular stomatitis virus

Vesicular stomatitis virus (VSV) is a rhabdovirus, consisting of 5 genes encoded by a negative sense, single-stranded RNA genome. In nature, VSV infects insects as well as livestock, where it causes a relatively localized and non-fatal illness. The low pathogenicity of this virus is due in large part to its sensitivity to interferons, a class of proteins that are released into the tissues and bloodstream during infection. These molecules activate genetic anti-viral defence programs that protect cells from infection and prevent spread of the virus. However, in 2000, Stojdl, Lichty et al.[50] demonstrated that defects in these pathways render cancer cells unresponsive to the protective effects of interferons and therefore highly sensitive to infection with VSV. Since VSV undergoes a rapid cytolytic replication cycle, infection leads to death of the malignant cell and roughly a 1000-fold amplification of virus within 24h. VSV is therefore highly suitable for therapeutic application, and several groups have gone on to show that systemically administered VSV can be delivered to a tumour site, where it replicates and induces disease regression, often leading to durable cures.[51][52][53][54] Attenuation of the virus by engineering a deletion of Met-51 of the matrix protein ablates virtually all infection of normal tissues, while replication in tumour cells is unaffected.[51]

Recent research has shown that this virus has the potential to cure brain tumours, thanks to its oncolytic properties.[55]


Main article: PVSRIPO

Poliovirus is a natural neuropathogen, making it the obvious choice for selective replication in tumours derived from neuronal cells. Poliovirus has a plus-strand RNA genome, the translation of which depends on a tissue-specific internal ribosome entry site (IRES) within the 5' untranslated region of the viral genome, which is active in cells of neuronal origin and allows translation of the viral genome without a 5' cap. Gromeier et al. (2000)[56] replaced the normal poliovirus IRES with a rhinovirus IRES, altering tissue specificity. The resulting PV1(RIPO) virus was able to selectively destroy malignant glioma cells, while leaving normal neuronal cells untouched.[57]


Reoviruses, an acronym for respiratory enteric orphan virus, generally infect mammalian respiratory and bowel systems. Most people have been exposed to reovirus by adulthood; however, the infection does not typically produce symptoms. The link to the reovirus' oncolytic ability was established after it was discovered to reproduce well in various cancer cell lines and lyses these cells.[58]

Reolysin is a formulation of reovirus that is currently in clinical trials for the treatment of various cancers.[59]


Senecavirus, also known as Seneca Valley Virus, is a naturally occurring wild-type oncolytic picornavirus discovered in 2001 as a tissue culture contaminate at Genetic Therapy, Inc. The initial isolate, SVV-001, is being developed as an anti-cancer therapeutic by Neotropix, Inc. under the name NTX-010 for cancers with neuroendocrine features including small cell lung cancer and a variety of pediatric solid tumours.


Main article: RIGVIR

In the 1960s, a group of scientists in Latvia led by Dr. Aina Muceniece studied oncolytic activity of ECHO viruses, but in 1968 a clinical trial of 5 ECHO enterovirus strains began (in trials participated stage-IV cancer patients volunteers). Scientists decided to continue researching ECHO-7 strain of ECHO virus (later called RIGVIR), because it showed the most pronounced oncolytic properties. III-phase trials started in 1988 with the aim to compare effect of RIGVIR therapy with results of chemotherapy and radiation therapy. In 2004 RIGVIR was patented and registered in Latvia and since then it has been used in cancer therapy.[19] RIGVIR virus was approved in Georgia in February 2015,[12] but in 2016 it was approved also in Armenia. Recent retrospective study published in Melanoma Research revealed that IB-IIC melanoma patients treated with oncolytic virus RIGVIR were 4.39–6.57-fold lower mortality than those, who according to melanoma treatment guidelines did not receive virotherapy and were only observed.[60] In 2015 Rigvir was included into the Latvian National guidelines for treatment of skin cancer and melanoma, developed by the Riga Eastern Clinical University Hospital Task Force.[61] In July 2016 new positive results were published in APMIS journal about RIGVIR efficacy in treatment of lung cancer and histiocytic sarcoma.[62]

Semliki Forest virus

Semliki Forest virus (SFV) is a virus that naturally infects cells of the central nervous system and causes encephalitis. A genetically engineered form has been pre-clinically tested as an oncolytic virus against the severe brain tumour type glioblastoma. The SFV was genetically modified with microRNA target sequences so that it only replicated in brain tumour cells and not in normal brain cells. The modified virus reduced tumour growth and prolonged survival of mice with brain tumours.[63] The modified virus was also found to efficiently kill human glioblastoma tumour cell lines.[63]


The maraba virus, first identified in Brazilian sandflies, is being tested clinically.[64][65]

Engineering oncolytic viruses

Directed evolution

An innovative approach of drug development termed "directed evolution" involves the creation of new viral variants or serotypes specifically directed against tumour cells via rounds of directed selection using large populations of randomly generated recombinant precursor viruses. The increased biodiversity produced by the initial homologous recombination step provides a large random pool of viral candidates which can then be passed through a series of selection steps designed to lead towards a pre-specified outcome (e.g. higher tumor specific activity) without requiring any previous knowledge of the resultant viral mechanisms that are responsible for that outcome. The pool of resultant oncolytic viruses can then be further screened in pre-clinical models to select an oncolytic virus with the desired therapeutic characteristics.[66]

Directed evolution was applied on human adenovirus, one of many viruses that are being developed as oncolytic agents, to create a highly selective and yet potent oncolytic vaccine. As a result of this process, ColoAd1 (a novel chimeric member of the group B adenoviruses) was generated. This hybrid of adenovirus serotypes Ad11p and Ad3 shows much higher potency and tumour selectivity than the control viruses (including Ad5, Ad11p and Ad3) and was confirmed to generate approximately two logs more viral progeny on freshly isolated human colon tumour tissue than on matching normal tissue.[66]


Attenuation involves deleting viral genes, or gene regions, to eliminate viral functions that are expendable in tumour cells, but not in normal cells, thus making the virus safer and more tumour-specific. Cancer cells and virus-infected cells have similar alterations in their cell signalling pathways, particularly those that govern progression through the cell cycle.[67] A viral gene whose function is to alter a pathway is dispensable in cells where the pathway is defective, but not in cells where the pathway is active.

The enzymes thymidine kinase and ribonucleotide reductase in cells are responsible for DNA synthesis and are only expressed in cells which are actively replicating.[68] These enzymes also exist in the genomes of certain viruses (E.g. HSV, vaccinia) and allow viral replication in quiescent(non-replicating) cells,[69] so if they are inactivated by mutation the virus will only be able to replicate in proliferating cells, such as cancer cells.

Tumour targeting

There are two main approaches for generating tumour selectivity: transductional and non-transductional targeting.[citation needed]

  • Transductional targeting involves modifying the viral coat proteins to target tumour cells while reducing entry to non-tumour cells. This approach to tumour selectivity has mainly focused on adenoviruses and HSV-1, although it is entirely viable with other viruses.[citation needed]
  • Non-transductional targeting involves altering the genome of the virus so it can only replicate in cancer cells, most frequently as part of the attenuation of the virus.[citation needed]
    • Transcription targeting can also be used, where critical parts of the viral genome are placed under the control of a tumour-specific promoter. A suitable promoter should be active in the tumour but inactive in the majority of normal tissue, particularly the liver, which is the organ that is most exposed to blood born viruses. Many such promoters have been identified and studied for the treatment of a range of cancers.[citation needed]
    • Similarly, viral replication can be finely tuned with the use of microRNAs (miRNA) artificial target sites or miRNA response elements (MREs). Differential expression of miRNAs between healthy tissues and tumors permit to engineer oncolytic viruses detargeted from certain tissues of interest while allowing its replication in the tumor cells.

Double targeting with both transductional and non-transductional targeting methods is more effective than any one form of targeting alone.[70]

Further information: Oncolytic adenovirus

Reporter genes

Viral luciferase expression in a mouse tumour

Both in the laboratory and in the clinic it is useful to have a simple means of identifying cells infected by the experimental virus. This can be done by equipping the virus with 'reporter genes' not normally present in viral genomes, which encode easily identifiable protein markers. One example of such proteins is GFP (Green fluorescent protein) which, when present in infected cells, will cause a fluorescent green light to be emitted when stimulated by blue light.[71][72] An advantage of this method is that it can be used on live cells and in patients with superficial infected lesions, it enables rapid non-invasive confirmation of viral infection.[73] Another example of a visual marker useful in living cells is luciferase, an enzyme from the firefly which in the presence of luciferin, emits light detectable by specialized cameras.[71]

Vaccinia virus infected cells expressing beta-glucuronidase (blue colour)

The E. coli enzymes beta-glucuronidase and beta-galactosidase can also be encoded by some viruses. These enzymes, in the presence of certain substrates, can produce intense colored compounds useful for visualizing infected cells and also for quantifying gene expression.

Modifications to improve oncolytic activity

Oncolytic viruses can be used against cancers in ways that are additional to lysis of infected cells.

Suicide genes

Viruses can be used as vectors for delivery of suicide genes, encoding enzymes that can metabolise a separately administered non-toxic pro-drug into a potent cytotoxin, which can diffuse to and kill neighbouring cells. One herpes simplex virus, encoding a thymidine kinase suicide gene, has progressed to phase III clinical trials. The herpes simplex virus thymidine kinase phosphorylates the pro-drug, ganciclovir, which is then incorporated into DNA, blocking DNA synthesis.[74] The tumour selectivity of oncolytic viruses ensures that the suicide genes are only expressed in cancer cells, however a 'bystander effect' on surrounding tumour cells has been described with several suicide gene systems.[75]

Suppression of angiogenesis

Angiogenesis (blood vessel formation) is an essential part of the formation of large tumour masses. Angiogenesis can be inhibited by the expression of several genes, which can be delivered to cancer cells in viral vectors, resulting in suppression of angiogenesis, and oxygen starvation in the tumour. The infection of cells with viruses containing the genes for angiostatin and endostatin synthesis inhibited tumour growth in mice. Enhanced antitumour activities have been demonstrated in a recombinant vaccinia virus encoding anti-angiogenic therapeutic antibody and with an HSV1716 variant expressing an inhibitor of angiogenesis.[76][77]


Adenoviral NIS gene expression in a mouse tumour (Located at the crosshairs) following intravenous delivery of virus (Left) compared to an uninfected control mouse (Right)

Addition of the sodium-iodide symporter (NIS) gene to the viral genome causes infected tumour cells to express NIS and accumulate iodine. When combined with radioiodine therapy it allows local radiotherapy of the tumour, as used to treat thyroid cancer. The radioiodine can also be used to visualise viral replication within the body by the use of a gamma camera.[71] This approach has been used successfully preclinically with adenovirus, measles virus and vaccinia virus.[78][79][80]

Approved therapeutic agents

Clinical research

In 2014-2016 period a number of clinical trials were initiated for a wide range of oncolytic virus products, reflecting the ongoing clinical development of this class of therapy.[86]

Ad5-yCD/mutTKSR39rep-hIL12 Prostate carcinoma I Recruiting Intraprostatic As single agent NCT02555397
Cavatak Bladder carcinoma I Recruiting Intravesical Optionally combined with low-dose mitomycin C NCT02316171
  Melanoma I Recruiting Intratumoral Combined with ipilimumab NCT02307149
          Combined with pembrolizumab NCT02565992
CG0070 Bladder carcinoma II No longer available Intravesical As single agent NCT02143804
      Recruiting Intravesical As single agent NCT02365818
DNX-2401 Brain tumors I Recruiting Intratumoral Combined with IFNγ NCT02197169
G207 Brain tumors I Not yet recruiting Intratumoral Optionally combined with radiation therapy NCT02457845
GL-ONC1 Ovarian cancer Ib Recruiting Intraperitoneal As single agent NCT02759588
HF10 Melanoma II Recruiting Intratumoral Combined with ipilimumab NCT02272855
  Solid tumors I Recruiting Intratumoral As single agent NCT02428036
Imlygic® Hepatocellular carcinoma I Not yet recruiting Intratumoral As single agent NCT02509507
  Melanoma n.a. Enrolling by invitation Intratumoral As single agent NCT02173171
    II Recruiting Intratumoral As single agent NCT02366195
          Combined with surgery NCT02211131
    III Active, not recruiting Intratumoral Combined with pembrolizumab NCT02263508
      Available Intratumoral As single agent NCT02147951
  Soft tissue sarcoma I/II Recruiting Intratumoral Combined with radiotherapy NCT02453191
JX-594 Hepatocellular carcinoma III Not yet recruiting Intratumoral Combined with sorafenib NCT02562755
MG1-MA3 Solid tumors I/II Recruiting Intravenous Combined with a MAGEA3-encoding adenovirus NCT02285816
MV-NIS Gynecological tumors II Recruiting Intraperitoneal As single agent NCT02364713
  Multiple myeloma II Recruiting Intravenous Combined with cyclophosphamide NCT02192775
OBP-301 Solid tumors I Not yet recruiting Intratumoral As single agent NCT02293850
Reolysin® Brain tumors I Recruiting Intravenous Combined with GM-CSF s.c. NCT02444546
  Multiple myeloma I Recruiting Intravenous Combined with dexamethasone plus a proteasomal inhibitor NCT02101944
Toca 511 Brain tumors II/III Not yet recruiting Intratumoral Combined with 5-FC and standard chemotherapy NCT02414165
  Solid tumors I/II Recruiting Intratumoral Intravenous Combined with 5-FC NCT02576665

Abbreviations: 5-FC, 5-fluorocytosine; GM-CSF, granulocyte macrophage colony-stimulating factor; IFNγ, interferon γ; MAGEA3, melanoma antigen family A3; s.c.,sub cutem.*initiated between 2014, March 1 and 2015, October 31.

Approved somewhere

  • Talimogene laherparepvec was approved by the US FDA in 2015, with the brand name Imlygic, for the treatment of melanoma in patients with inoperable tumors.[82] In Jan 2016 it was approved in Europe for some inoperable melanoma.[87]
  • Oncorine, by Shanghai Sunway Biotech, was approved in China for Head and neck cancer in 2005.[88] It is based on the adenovirus H101.
  • RIGVIR, approved for melanoma treatment in Latvia (2004), Georgia (2015) and Armenia (2016) for melanoma treatment.

Started phase III

  • Reolysin, by Oncolytics Biotech, is in phase III for head and neck cancer.[89] An interim data release showed that this phase III had already obtained statistically significant tumor shrinkage in patients at their 6-week scan,[90] although the trial will not be complete until the overall survival data matures. Encouraging early results in colorectal cancer.[91][92] In total there are 31 clinical studies either completed or ongoing, including many testing Reolysin alongside standard chemotherapies in a variety of solid cancers.[93]

Started phase II

  • JX-594, by Jennerex, is currently in phase II for hepatocellular carcinoma.[94] JX-594 is a thymidine kinase-deleted Vaccinia virus plus GM-CSF.[95][96]
  • Seneca Valley virus (NTX-010) and (SVV-001), oncolytic picornavirus, is in phase II for small cell lung cancer and neuroblastoma.[9][88][97][98]
  • ColoAd1 was developed by Psioxus Therapeutics Ltd using the process of directed evolution. ColoAd1 has successfully completed recruitment in a Phase I clinical trials of ColoAd1.[citation needed] The trial involved recruiting patients with metastatic solid tumours where no standard treatment options were applicable. Samples from these patients showed evidence of virus replication within tumour sites after intravenous delivery. The second phase of the ColoAd1 study is planned to commence in 2014 and will examine efficacy in patients with metastatic colorectal cancer. Unlike many other oncolytic viruses, ColoAd1 can be administered by intravenous injection rather than requiring intra-tumoral injection. A second trial is comparing the efficacy of the intravenous approach versus direct intra-tumoural injection to assess the most effective method of delivering ColoAd1 to cancer patients (see the EU Clinical Trials Register for further details). A third trial is examining the intra-peritoneal route of delivery for women with late stage ovarian cancer.
  • Cavatak[99][100] is a coxsackie virus which is in phase II clinical trials for the treatment of malignant melanoma.[101]

Started phase I

  • SEPREHVIR (HSV-1716), by Virttu Biologics,[102] completed phase I in glioblastoma, in squamous cell carcinoma of head and neck, and in melanoma. Ongoing phase I dose escalation study of intratumoral HSV-1716 in pediatric/young adult patients with non–central nervous system solid tumours and a new phase I/IIa study in mesothelioma commenced in 2012.[103][104]
  • CGTG-102 (Ad5/3-D24-GMCSF), by Oncos Therapeutics,[105] while in phase I was already used to treat 200 advanced cancer patients in the company's Advanced Therapy Access Program.[106]
  • GL-ONC1, by Genelux, is in phase Ib administered intravenously for solid tumours.[107] Additional trials are ongoing utilising alternative methods of administration including intrapleural administration for patients with malignant pleural effusion,[108] intraperitoneal injection for patients with advanced peritoneal carcinomatosis,[109] intraperitoneal injection for recurrent ovarian cancer,[110] and intravenous injection in combination therapy in head and neck cancers.[111]
  • MV-NIS, an engineered measles virus has shown to be effective in targeted destruction of myeloma plasma cells. Radioactive Iodine imaging provides a novel technique for NIS gene expression monitoring.[112]
  • DNX-2401 is an oncolytic adenovirus with US Orphan drug status for glioma.[113]
  • ONCOS-102 is an engineered human serotype 5/3 adenovirus coding for human GM-CSF optimized to induce systemic anti-tumor T cell response in cancer patients. It has completed a phase I trial and is starting another for malignant pleural mesothelioma (MPM).[114]

Oncolytic viruses in conjunction with existing cancer therapies

It is in conjunction with conventional cancer therapies that oncolytic viruses have often showed the most promise, since combined therapies operate synergistically with no apparent negative effects.[115]

Clinical trials

Onyx-015 underwent trials in conjunction with chemotherapy before it was abandoned in the early 2000s. The combined treatment gave a greater response than either treatment alone, but the results were not entirely conclusive.[116] Hepres simplex virus, adenovirus, reovirus and murine leukemia virus are also undergoing clinical trials as a part of combination therapies.[117]

Pre-clinical research

Chen et al. (2001)[118] used CV706, a prostate-specific adenovirus, in conjunction with radiotherapy on prostate cancer in mice. The combined treatment resulted in a synergistic increase in cell death, as well as a significant increase in viral burst size (the number of virus particles released from each cell lysis). No alteration in viral specificity was observed.

SEPREHVIR (HSV-1716) has also shown synergy in pre-clinical research when used in combination with several cancer chemotherapies.[119][120]

The anti-angiogenesis drug Bevacizumab (anti-VEGF antibody) has been shown to reduce the inflammatory response to oncolytic HSV and improve virotherapy in mice.[121]

In fiction

In science fiction, the concept of an oncolytic virus was first introduced to the public in Jack Williamson's novel Dragon's Island, published in 1951, although Williamson's imaginary virus was based on a bacteriophage rather than a mammalian virus.[122] Dragon's Island is also known for being the source of the term "genetic engineering".[123]

The plot of the Hollywood film I Am Legend is based on the premise that a worldwide epidemic was caused by a viral cure for cancer.[citation needed]

See also


Further reading

  • Harrington, Vile, Pandha (2008). Viral Therapy of Cancer. Hoboken, N.J.: Wiley. ISBN 0470019220.
  • Thorne, Kirn, Liu (2011). Oncolytic Viruses: Methods and Protocols (Methods in Molecular Biology). New York: Humana Press. ISBN 1617793396.
  • Sinkovics (2005). Viral therapy of human cancers. New York: Dekker. ISBN 0824759133.

External links

Therapeutic Substance(s): 
Therapeutic intervention: 

Ozone Therapy


Ozone Therapy Information, Ozone Therapy Articles, and Ozone Therapy Studies

Ozone Therapy Summary: (from
Ozone Therapy is a medical therapy that has been used worldwide for over 50 years with dramatic success and safety. In North America Ozone Therapy has not yet been fully recognized by the medical authorities, however if you review our ever growing list of Ozone Doctors, you will see that it is being adopted more and more by formally 'traditional' medical practitioners. It is clear that Ozone Therapy works, and it is becoming one of the most useful tools in medical clinics across America and around the World. (See "A Review of Ozone Therapy Applications" to learn how ozone is being administered). If you are completely new to Ozone and are wondering what all the fuss is about, read our new section Ozone Therapy Basics and then come back to these articles.

What does it do? To breifly summarize, ozone accomplishes these very important tasks in your body:

1/ Ozone is AntiAging (some of those AntiAging effects can be attributed to the following list of actions...)
2/ Ozone Increases Oxygenation of your Cells (it has been proven that cancer and disease grow in poorly oxygenated tissues in your body).
3/ Ozone Modulcates your Immune System (for those with a weakened immune system, Ozone will boost the immune system. For those with Auto-Immune Disorders, Ozone will modulate the immune system to help to stop it from attacking healthy human cells.)
4/ Ozone Increases Energy Production in your Cells (your cells need energy to be healthy; low energy levels mean that you and your cells will not be healthy and will age)
5/ Ozone Increases the Activity of your "Anti-Oxidant Enzyme Systems". This means ozone will reduce the oxidation levels of your body.
6/ Ozone Reduces the level of acidity of your body (never mind the Alkaline Water...use Ozone!)
7/ Ozone kills Bacteria, Viruses (and virtually all other disease causing organisms) on contact
8/ Ozone Kills Cancer cells on contact

The IOA - The International Ozone Association holds International Ozone Congresses every two years in various locations around the world. AEPROMO - The Spanish Association of Medical Professionals in Ozone Therapy also holds World Ozone Congresses every two years. The recent Ozone Congress held June 2012 in Madrid Spain attracted Ozone Therapy Doctors from 25 countries around the world! Countries such as Brazil, Germany, Russia, Spain, Italy, Turkey, Austria, and even the USA all have their own Ozone Thearpy Associations which hold yearly conventions (Congresses) where physicians from around the world attend to present their new findings, new procedures, and results of new studies. In 2009 there was a very public announcement in Toronto Canada, an announcement that shook the world when everyday "allopathic" medical doctors openly announced that Ozone not only can ozone be used to successfully treat herniated discs, but the studies indicate that Ozone Therapy works far better than traditional surgery!

The word is out and the door is open. Whether you are already knowledgeable about Ozone and know its value in medicine, or whether you are a skeptic, you will enjoy this site on Ozone Therapy. Review the articles posted here, learn about how ozone works, take a course from one of our many Ozone Courses. Learn.

Read the articles in this section to find out how Ozone Therapy may help you!

Psorinum, the anti cancer miracle from India.

At the ASCO(American Society of Clinical Oncology) congress in Chicago from June 4th to 8th 2010, the world's most prestigious congress of clinical oncology with 30 to 35,000 participants, was published on the poster section a rather sensational result in the treatment of non-small cell lung cancer with an increase of five year survival from an expected <1% to 44%!!
There are also extremely good results in the treatment of gastro.intestinal cancers.
by Aradeep Chtterjee et al from Calcutta, India.
Although, great advances have been made in the treatment of some forms of cancer and new advances in surgery, radiotherapy, and chemotherapy leading to an increase in cure rates have been achieved, such interventions are often too much expensive and beyond the reach of many cancer patients of the developing as well as of the developed countries. In developing countries, majority of the cancer patients have inadequate access to the mainstream cancer treatments due to lack of proper medical infrastructures, skills, and above all limited financial resources.
Some types of cancer (i.e., liver, gall bladder, pancreatic, and stomach) are still associated with poor prognosis to conventional cancer treatments.
Side effects of the chemotherapy and radiation therapy are also intolerable to many cancer patients. In most of the situations, elderly cancer patients cannot be provided with conventional cancer treatments because of old age-related problems . As a result, alternative cancer treatments have become an important feature of oncology regardless of geographic region and they appear to exist in greater abundance through out the world. Many alternative cancer therapeutic modalities are now being practiced in India, and one of them which has gained significant popularity is called Psorinum Therapy .
The investigational anticancer drug used in this alternative cancer therapy is “Psorinum” which is derived from the sphere of homeopathy. The supportive treatments of Psorinum Therapy are adopted both from the spheres of allopathy and homeopathy. Psorinum is an alcoholic extract of the scabies, slough, and pus cells. According to the pre-clinical data, “Psorinum-6x” (“x” stands for decimal potency of homeopathy) activates different immune effector cells (e.g., T cells, and accessory cells like, macrophages, dendritic cells, and natural killer cells) which can trigger a complex antitumor immune response . In a rat model study, daily oral administration of Psorinum 6x at doses up to 0.5 ml/Kg body weight/day for 2 weeks resulted in no adverse side effect  Published retrospective and prospective studies also support the efficacy of Psorinum Therapy in treating patients with various malignancies.
In an observational, open level and single arm study on158 patients with histologically confirmed stomach, gall bladder, liver and pancreatic cancer, complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) of cases The participants' eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum-6x was administered orally to all the participants up to 0.02ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. There were 42 stomach cancers, 40 gall bladder cancers, 44 pancreatic cancers and 32 liver cancers included in the final analysis of the study. 
Some other homeopathic medicines were also used for supportive care:
Table 1
Details of the frequently used homeopathic medicines for the purpose of the supportive cares.
NameOriginDosingPowerUsed to control ailments
(1) Chelidonium majus Herb-Chelidonium majus Up to 0.04 ml/Kg body weight/day orally Mother tincture (1) Abnormal liver functions
 (2) Dysponea
(2) Carduus marianus Herb-Carduus marianus Up to 0.04 ml/Kg body weight/day orally Mother tincture (1) Abnormal liver function
 (2) Cholestasis
(3) Baryta carbonica Barium carbonate Up to 0.02 ml/Kg body weight/day orally 200c (1) Anaemia
 (2) Cancer-related pain
(4) Conium maculatum Herb-Conium maculatum Up to 0.02 ml/Kg body weight/day orally 200c (1)Heart troubles
(2) Abnormal blood pressure
(5) Carbo animalis Animal charcoal Up to 0.02 ml/Kg body weight/day orally 200c (1) Cough
(2) Constipation
(6) Bryonia alba Herb-Bryonia alba Up to 0.02 ml/Kg body weight/day orally 200c (1) Dysponea
(2) Cancer-related pain
(7) Medorrhinum Gonorrhoeal cocci Up to 0.02 ml/Kg body weight/day orally 200c (1) Abnormal blood sugar
(2) Cancer-related pain
(8) Thuja occidentalis Herb-Thuja occidentalis Up to 0.02 ml/Kg body weight/day orally Mother tincture (1) Abdominal distension
(2) Electrolytic imbalance
(9) Cholesterinum Cholesterine Up to 0.02 ml/Kg body weight/day orally 200c (1) Abnormal liver function
(2) Cholestasis
(10) Lycopodium clavatum Herb-Lycopodium clavatum Up to 0.02 ml/Kg body weight/day orally 200c (1) Abdominal distension
(2) Cancer-related pain
 (5.95%) participants were dropped out from the study as they opted for conventional cancer treatments, among them 4 of stomach, 2 of gall bladder, 3 of pancreatic, and 1 of liver cancers.  Among the 158 participants, 84 (53.16%) were male and 74 (46.84%) were female. According to the AJCC TNM staging system, 39 (24.68%) were diagnosed at stage-III, and 112 (70.89%) were diagnosed at stage-IV. The participants' Karnofsky status was between 40–70%, and Eastern Cooperative Oncology Group (ECOG) status was between 2-3. Among the 39 participants (24.68%) who were diagnosed at stage-III, 13 (33.33%) had complete response and 16 (41.03%) had radiological partial response. Among the 112 (70.89%) participants who were diagnosed at stage-IV, 12 (10.71%) had radiological complete response and 38 (33.93%) had radiological partial response
In this study, no adverse side effects were observed from the drug Psorinum. However, very few patients reported to have mild oral irritation and skin itching which were successfully controlled by the supportive cares. Psorinum Therapy was also effective in improving the disease symptoms and the quality of life of the participants. At least 60% participants of stage-III and at least 45% participants of stage-IV reported that the therapy was effective in reducing their cancer-related pain, cough, dysponea, nausea and vomiting, fatigue, constipation and improving appetite, and weakness. These were also confirmed after examining the participants clinically. Improvements were also observed in the lab investigations like Complete Blood Count (CBC), Liver Function Test (LFT), Kidney function test, AFP level, and CA 19.9. These lab investigations were done as a part of their routine clinical check ups. Among the 158 participants, 98 (62.03%) were aged 65 years or more. Better outcomes were observed among the participants below 65 years of age than the participants who were over the age of 65. The outcomes did not vary significantly while considering gender.
Table 2
TNM Staging, partial and complete tumor response in each cancer type.
Primary cancer typesNo. of participantsTNM Staging of the participantsNo. of patients: Complete tumor response occurredNo. of patients: Partial tumor response occurred
Diagnosed at stage-II and stage-IIIDiagnosed at stage-IV
Stomach 42 11 31 6 (14.29%) 16 (38.1%)
G. Bladder 40 13 27 7 (17.5%) 17 (42.5%)
Pancreas 44 9 35 8 (18.18%) 13 (29.55%)
Liver 32 13 19 7 (21.87%) 10 (31.25%)
Table 3
Survival outcomes in each cancer type.
Primary organ affectedNo. of PatientsMaleFemaleSurvived at least 1 yearSurvived at least 2 yearsSurvived at least 3 yearsSurvived at least 4 yearsSurvived at least 5 years
Stomach 42 22 20 34 24 21 20 16 (38.1%)
G. Bladder 40 21 19 32 25 20 18 15 (37.5%)
Pancreas 44 24 20 34 28 27 21 17 (38.64%)
Liver 32 17 15 26 22 19 17 14 (43.75%)
The cumulative 5-year survival was 39.24% for patients who received Psorinum treatment, compared with an estimated 5-year survival of 23% for stomach cancer, 10% for liver cancer, <4% for pancreatic cancer and <15% for gall bladder cancer for patients taking conventional therapies. 28 patients (17.72%) had a complete recovery from their cancer in this study.
Psorinum in the treatment of Non Small Cell Lung Cancer(NSCLC)
In another phase II, open-level, single arm, and single stage  study, also performed by Dr Chatterje et al, 95 participants were included with NSCLC.
According to the AJCC TNM staging system, 58 (61.05%) of them diagnosed at stage IV. According to the RECIST criteria, complete tumor
response occurred in 19 (20%) cases and partial tumor response occurred in 28 (29.47%) cases. 82 (86.32%) of them survived at least 1 yr, 70
(73.68%) survived at least 2 yrs, 58 (61.05%) survived at least 3 yrs, 49 (51.58%) survived at least 4 yrs, and 42 (44.21%) of them survived at
least 5 yrs. These participants did not receive chemotherapy, radiation therapy, or any other investigational cancer treatments. Participants
reported no side effects from the drug psorinum.
Regarding pancreatic cancer:
44 patients participated in the study with Psorinum D6, 0,02 ml per kg body weight in the morning on empty stomach. Survival after first year 34,
after 2 years 28, after 3 years 27, after 4 years 21, and after 5 years 17 of the patients were still alive, equal to a 5-year survival of 39% - Probably the highest ever recorded 5 yearr survival on Pancreatic  Cancer published so far in medicine history!!
These results were examined by a very critical an independent expert commission at the National Cancer Institute in Bethesda, near Washington DC, USA, who has accepted the results, so that Dr. Chatterjee was able to present the results at the ASCO conference. There are plans to make more research on Psorinum on the famous MD Andersson Cancer Institute in Houston,  Texas, USA
The treatment is suitable for many more cancer types, but research has so far been focused on the more difficult cancers.
Dr Mikael Nordfors has been treating a few patients in Europe with Psorinum, with similar results as in India. He also combines psorinum treatment with GcMAF, LDN, Cancer psychotherapy and other immune strengthening treatments
Some of these case stories are published below.
Therapeutic Substance(s): 
Therapeutic intervention: 

Todoxin, the immune stimulant from Serbia


From, and

Issue 11/1998 of 08/06/1998
Introductory remark

In regard with so called "alternative" medicaments there has been a discussion going on for some time about a preparation called "TODoXIN". There is too little information on the effectiveness of this preparation, but the articles are circulating on the topic of "the medicine: 'TODoXIN'" expressing excitement or rejection. As far as we know, there are no underpinned contributions in which all the knowledge would be critically worked out and summarized. By the following detailed article we wish to fill this gap.


"TODoXIN" is a herbal remedy which has been applied on over 7,000 patients in the cases of different (oncogen) viruses and against HIV-infection effects for 10 years. It was developed by Dr. Todor Jovanovic, a physician born in Vrani Do, Kosovo, in 1935. Dr. Jovanovic studied medicine in Belgrade and finished his specialization in Allergology. After the graduation he carried out research in the UN Research Centre for Nuclear Medicine and in military research centre in Vinca, near Belgrade. The main field of the research was search for histocompatible materials for implantats. Another field of intensive work was the research and monitoring of immunostimulating effects of plant extracts.

In 1987, Dr. Jovanovic applied for a patent on TODoXIN recipe. After that, he made an effort to get the support of experts and institutions in the country and abroad for his projects. There were, among others, the president of Serbian Academy of Science and Art, Dusan Kanazir, Luk Montagnier, the man who discovered HIV, as well as the leader of the special program of WHO for AIDS, Jonathan Man.

Because of the sparse data, no one showed interest for that project, except for the leader of a research group from Austria. With the Austrian partners in the research, Dr. Jovanovic signed a long-term contract on cooperation in 1988. The goal of the cooperation was to test the remedy on the international scale, galenic development and later, submission of the appropriate study results, obtaining the international approval and production.

After it has been proved toxicologically safe in 1988, the Austrian team, in collaboration with the Karolinska Institute for Immunology in Stockholm, in 1988-89, succeeded in showing the immunostimulating properties of TODoXIN in vitro, as well as the development of pharmacodynamic model of effect mechanisms induced on the immuoendocrinal level. That model could have been tested ex vitro and and confirmed in vivo. It was followed by intensive medical observation of its use, in collaboration with some clinical workers and physicians, in a wide spectrum of potential indications for immunostimulating properties of TODoXIN. On the basis of the data obtained by early 1991, the scientists of National Institutes of Health (NIH), in Washington, expressed their readiness to examine TODoXIN in vitro within the "Developmental Therapeutics Program". The studies of HIV culturing proved that cell bearable concentrations of active agents of TODoXIN can inhibit HIV up to 100%.

At the end of 1991 TODoXIN was given the license for production in Yugoslavia under the register number 4684 dd 31/10/88, as a "dietetic product based on honey and medicinal herbs ". The records on HIV- inhibiting capacity of TODoXIN, obtained at NIH, as well as the results of HIV-positive patients treated with TODoXIN since 1988, were not presented until the 10th International Conference on AIDS in Yokohama (1994), because NIH which was late in giving the permission for releasing the data.

On the basis of these data the Austrian research group succeeded in winning over the European virologists and AIDS researchers, prof. Richard Teddar and Dr. Clive Loveday from UCL Medical School of London, to the scientific collaboration. The data jointly won over the years that followed were appraised and designated as “very promising" by members of the British Medical Research Council – MRC and HIV Clinical Trial Centre – prof. A. Brackenridge, prof. D. Jeefries, prof. I. Weller and Dr J. Darbyshire.

On the 11. International AIDS Conference in Vancouver (1996), an official symposium on TODoXIN was held, where the most recent data were presented.

After that, the Department for Retro virology of Royal Free Medical School in London came up with offer to carry out further studies in England under official supervision of pharmaceutical authorities, MRC and one ethical committee. The results of these studies were supposed to support the official request for registration of TODoXIN in the European Union. The study started, after longer preparations, in September 1997, after it had been established that TODoXIN is to be produced in the future by Dr. Jovanovic together with an Austrian partner in the research, within one Austrian firm.

In the course of the study, Dr. Jovanovic decided to accept the offers of English researchers and their American partners to have TODoXIN produced in the USA in the future and to carry out further study over there. In order to present data which were up-to-date in 1998. to American partners, the London study, started in 1997, was interrupted in March 1998, and a new study was started, using the first laboratory samples of American TODoXIN. A separate American study is still about to start this year in California. Therefore, for the precaution sake, no new TODoXIN data were presented in the 12th International AIDS Conference in Geneva.


TODoXIN is made exclusively of plants and does not contain any synthetic components and preservatives.

Plants or parts of plants which are used for preparation are regularly tested for toxins which naturally occur, and for the presence of toxically substances used in agriculture (DDT, Lindan, Dieldrin, Endrin, Hexachlorbenzol, heavy metals, nitrites, nitrates, fungi, aerobic and anaerobic bacteria etc.)

In a joint poster session (abstract PA0340) presented by "TODoXIN Study Group" at 10th International AIDS Conference in Yokohama (1994) to the Department of Immunology of the Karolinska Institute (Sweden) and National Institutes of Health of the USA the composition of TODoXIN was presented in the following way:

"TODoXIN is a novel antiviral and immunostimulating preparation based upon an ion carrier molecule with specific binding affinities and a carrier specific substrate formulation. TODoXIN's formulation is unique in three aspects:

1. It comprises a very broad spectrum of physiologically active, cis-oriented and water soluble carbohydrates, carboxylic acids, vitamins, fat soluble vitamins, coenzymes and enzymes such as Amylases, Phosphates and Catalyses.

2. It contains both agonic and antagonic agents such as Ca and Fe, in physiologically relevant concentrations.

3. It contains a spectrum of minerals in permanent solution."

Micro-nutrients present in TODoXIN are exclusively of plant origin. They are obtained directly from fruits (mainly citrus fruits). Formulation also contains about 20 vol.-% honey.

Herbal active substance is kept in secret by Dr. Jovanovic. At present, there is a patent procedure running on the territory of the Former Yugoslavia. The exact composition, as well as pharmacokinetic data are not available for publication (not even in the editorial office). However, every therapeutic physician who would like to apply TODoXIN can have access to this data.

The up to date experience confirm the following indication:

myelo-proliferative syndrome


acute lymphoblast leukemia

acute myeloid leukemia

malignant lymphoma


testicular tumor, prostate, breast, rectum, cradle, lungs, skin and all gynecologist cancers.


There is hope even in case of very progressive diseases, like in lang metastasis, liver, bones. In many cases when patients were inoperable, because of diffusible infiltration of primary tumor into adjoining tissue and many metastasis even in case of bone decalcification, after TODOXIN therapy, the primary tumor is more clearly differentiated, looses in mass and becomes operable. Metastasis has disappeared, bones have been recalcificated and patients experienced complete remission. This phenomenon is 100 times more frequent than so called spontaneous remission in oncology practice.

However, it is most useful to start TODOXIN therapy as soon as the diagnosis has been established, for the effects are much better if it starts sooner. In progressive stadiums of cancer, a week can sometimes has the same significance as a whole year in different phases of cancer.


TODoXIN is in official use since 1963. Over 1300 HIV1 and 2 infected patients have been treated and the results are:

At patients whose virus serum was observed in short intervals, periodical appearance of HIV1 free virus (RNA virus serum) was noticed in the beginning of therapy during first 14 days of the high dose therapy cycles (taking every 2 hours).


There comes the increasing of 20 times above the average values and after that the gentle decreasing of virus serum which is on the detection limit (up to 4 log) in period between second and sixth week. Further on the value of virus serum constantly decreases (at detection limit, less than 20c/ml) after two to four cycles of the high dose therapy, that is 12-14 weeks.

After 6-18 months, the number of CD 4 cells increases for 50-150% of basic values and it happens with most patients. The time necessary for reaching and exceed the referent values is proportional to time extend of HIV infection before the therapy.

The significant changes during the therapy initiate the introduction of special forward therapy with corresponding dozes. This therapy deduces the clinical symptoms of viremia to minimum (to less than 2%).

Therapeutic Substance(s): 
Therapeutic intervention: