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Clinical and Immunologic Evaluation of Dendritic Cell–Based Immunotherapy in Combination With Gemcitabine and/or S-1 in Patients With Advanced Pancreatic Carcinoma

Kimura, Yukino MS*; Tsukada, Jun PhD*†; Tomoda, Takeshi MD; Takahashi, Hidenori MD; Imai, Kazuhiro PhD*; Shimamura, Kanae MMS*; Sunamura, Makoto MD, PhD§; Yonemitsu, Yoshikazu MD, PhD; Shimodaira, Shigetaka MD, PhD; Koido, Shigeo MD, PhD#; Homma, Sadamu MD, PhD‡**; Okamoto, Masato DDS, PhD*†‡

doi: 10.1097/MPA.0b013e31822398c6
Original Articles

Objectives In the current study, we have evaluated the clinical and immunological responses in patients with advanced pancreatic carcinoma who received dendritic cell (DC)–based immunotherapy in combination with gemcitabine and/or S-1.

Methods Dendritic cell–based immunotherapy (DC vaccine alone or DC vaccine plus lymphokine-activated killer [LAK] cell therapy) in combination with gemcitabine and/or S-1 has been carried out in 49 patients with inoperable pancreatic carcinoma refractory to standard treatment.

Results Of 49 patients, 2 patients had complete remission, 5 had partial remission, and 10 had stable disease. Prolongation of survival in this cohort was highly likely (median survival, 360 days). Survival of patients receiving DC vaccine and chemotherapy plus LAK cell therapy was longer than those receiving DC vaccine in combination with chemotherapy but no LAK cells. Increased numbers of cancer antigen-specific cytotoxic T cells and decreased regulatory T cells were observed in several patients on immunotherapy, but increased overall survival time tended to be associated only with the latter. None of the patients experienced grade 3 or worse adverse events during the treatment period.

Conclusions Dendritic cell vaccine–based immunotherapy combined with chemotherapy was shown to be safe and possibly effective in patients with advanced pancreatic cancer refractory to standard treatment.

From the *Research and Development Division, Tella Inc, Tokyo; †Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo; ‡Seren Clinic, Tokyo; §Department of Molecular Pathology, Tohoku University School of Medicine, Sendai; ∥R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka; ¶Cell Processing Center, Shinshu University Hospital, Nagano; and #Division of Gastroenterology and Hepatology, Department of Internal Medicine and **Department of Oncology, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.

Received for publication November 5, 2010; accepted May 9, 2011.

Reprints: Masato Okamoto, DDS, PhD, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishi-tokyo-shi, Tokyo, 202-8585, Japan (e-mail: mokamoto2009@gmail.com).

This investigation was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Foundation for Promotion of Cancer Research; and the Mitsui Life Social Welfare Foundation.

The authors declare no conflict of interest.

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.