Author(s): M. Okamoto,
S. Yusa, K. Shimamura, T. Ogawa, T. Tomoda; Musashino University,
Faculty of Pharmacy, Nishi-Tokyo-shi, Japan; Tella, Inc., Shinjuku-ku,
Japan; Seren Clinic, Minato-ku, Tokyo, Japan
Pancreatic cancer has a poor prognosis. Tumor-specific cytotoxic T
lymphocytes (CTLs) can be activated in vivo by dendritic cell
(DC)-based vaccination. However, clinical responses to the
immunotherapy with DC vaccination have only been observed in a minority
of patients with solid cancer. Combination with other treatment
modalities such as chemotherapy may overcome immunoresistance of cancer
cells. It has been shown previously that gemcitabine as well as S-1
sensitises human pancreatic carcinoma cells against CTL-mediated lysis.
In the current study, the clinical efficacy of the DC vaccine pulsed
with the peptide derived from pancreatic cancer-associated antigen in
combination with gemcitabine/S-1 has been evaluated in the patients
with advanced, inoperable pancreatic cancer.
patients with advanced, inoperable pancreatic cancer refractory to
standard treatment were entered the study. DCs that were generated from
CD14+ monocytes from leukapheresis by 6-day cultivation with
granulocyte macrophage-colony stimulating factor (GM-CSF) and
interleukin (IL)-4 were matured by OK-432, a streptococcal agent, and
were pulsed with the pancreatic cancer-associated antigen. These DCs (1
x 107) were intradermally administered 5 times at 14-day intervals
concomitantly combined with gemcitabine and/or S-1.
the 13 patients, complete response (CR) was observed in 2 (15.4%),
partial response (PR) in 7 (54.8%), stable disease (SD) in 2 (15.4%),
progressive disease (PD) in 2 (15.4%). Response rate was 69.2%.
Survival rate, quality of life, and performance status were markedly
increased. Severe side effects of more than grade 3 that were assessed
in accordance with NCI-Common Toxicity Criteria v.2.0, were not
Conclusions: It was strongly suggested that the DC
vaccination pulsed with cancer associated-peptid in combination with
gemcitabine and/or S-1 was safety and effective in the patients with
the inoperable pancreatic cancer refractory to standard treatment.
Dendritic cell-based vaccination in combination with gemcitabine/S-1 in patients with advanced pancreatic cancer. Sub-category:
Author(s): M. Okamoto,