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

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.