Transl Oncol. 2008 Jul;1(2):65-72.
Yamamoto N, Suyama H, Yamamoto N.
Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, Philadelphia, PA 19126-3305, USA.
Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Therefore, macrophages of prostate cancer patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent MAF (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages activated by GcMAF develop a considerable variation of receptors that recognize the abnormality in malignant cell surface and are highly tumoricidal. Sixteen nonanemic prostate cancer patients received weekly administration of 100 ng of GcMAF. As the MAF precursor activity increased, their serum Nagalase activity decreased. Because serum Nagalase activity is proportional to tumor burden, the entire time course analysis for GcMAF therapy was monitored by measuring the serum Nagalase activity. After 14 to 25 weekly administrations of GcMAF (100 ng/week), all 16 patients had very low serum Nagalase levels equivalent to those of healthy control values, indicating that these patients are tumor-free. No recurrence occurred for 7 years.
Comments
Mikael Nordfors
March 31, 2010 - 12:40pm
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Gc-MAF in treatment of
Gc-MAF in treatment of prostate cancer: Part II
From http://prostatecancerinfolink.net/2008/12/28/gc-maf-in-treatment-of-prostate-cancer-part-ii/
We have been kindly advised of the fact that the full text of the Yamamoto et al. paper on treatment of men with prostate cancer with Gc-MAF is available on line on the Translational Oncology web site.
In our prior commentary, based exclusively on the abstract of this paper, we had asked the following questions:
The full text allows us to answer many (but not all) of these questions.
As previously discussed, all patients were treated once weekly with 100 ng/ml of Gc-MAF for a period ranging from 14 to 25 weeks. Results following that treatment can now be fully summarized as follows:
What is one to make of this paper?
Well in the first place it would be naive to not to take it seriously. Something is clearly happening! And if at least one drug company doesn’t pick up on this research, I would be disappointed (but then that wouldn’t be the first time!) Secondly, it seems likely to me that some of the data not provided in this paper is available somewhere. We still don’t know, for example:
We are then faced with the question “What is a cure?” If these 16 men all really had stable disease for a minimum of 7 years, with no progression, and no other therapy following 14-25 weeks of Gc-MAF treatment, that certainly sounds like a remarkable outcome to me!
One last thing, just so that it is absolutely clear. Gc-MAF is not patient specific. In other words (unlike biologics like sipuleucel-T), it does not have to be extracted from the serum or tissues of the individual patient. In this trial, the serum required to make the Gc-MAF used to treat the patients was simply donated by members of the staff of the Socrates Institute.
Mikael Nordfors
November 23, 2014 - 9:54am
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This is most likely also relevant to this article:
Inconsistencies and questionable reliability of the publication “Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophages-activating, GcMAF” by Yamamoto et al
Rehder DS, Nelson RW, Borges CR (2009) Glycosylation status of vitamin D binding protein in cancer patients. Protein Sci 18:2036–2042