Dendritic cell-based vaccination in combination with gemcitabine/S-1 in patients with advanced pancreatic cancer. Sub-category:

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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
 
Abstract:
Background:
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.
 
Methods: Thirteen
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.
 
Results: Of
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
observed.
 
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.