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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Feb 6, 2016; 7(1): 133-138
Published online Feb 6, 2016. doi: 10.4292/wjgpt.v7.i1.133
Dendritic cell-based vaccine for pancreatic cancer in Japan
Masato Okamoto, Masanori Kobayashi, Yoshikazu Yonemitsu, Shigeo Koido, Sadamu Homma
Masato Okamoto, Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo 108-8641, Japan
Masato Okamoto, Oncology Cencer, Kitasato Institute Hospital, Tokyo 108-8641, Japan
Masanori Kobayashi, Seren Clinic Nagoya, Nagoya, Aichi 460-0008, Japan
Yoshikazu Yonemitsu, R and D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Shigeo Koido, Division of Gastroenterology and Hepatology, Department of Internal Medicine, the Jikei University School of Medicine, Kashiwa, Chiba 277-8567, Japan
Sadamu Homma, Department of Oncology, the Jikei University School of Medicine, Tokyo 105-8461, Japan
Author contributions: Okamoto M designed the aim of the editorial, wrote the manuscript and generated the figure; Kobayashi M, Yonemitsu Y, Koido S and Homma S contributed to the writing of the manuscript.
Conflict-of-interest statement: Yonemitsu Y is a previous member of the Board of Directors on Science and Medicine at tella Inc; all remaining authors have declared no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Masato Okamoto, DDS, PhD, Professor, Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. okamotom@pharm.kitasato-u.ac.jp
Telephone: +81-3-57916495 Fax: +81-3-34469036
Received: July 7, 2015
Peer-review started: July 7, 2015
First decision: July 31, 2015
Revised: August 28, 2015
Accepted: November 13, 2015
Article in press: November 17, 2015
Published online: February 6, 2016
Abstract

“Vaccell” is a dendritic cell (DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DC-maturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity (DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be “Responders” for the DC vaccine in advanced pancreatic cancer patients. We next conducted a small-scale prospective clinical study. In this trial, we pulsed HLA class II-restricted WT1 peptide (WT1-II) in addition to HLA class I-restricted peptide (WT1-I) into the DCs. Survival of the patients received WT1-I and -II pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-I or WT1-II alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progression-free survival as compared to the DTH negative patients. The activation of antigen-specific immune responses by DC vaccine in combination with standard chemotherapy may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan.

Keywords: Dendritic cell, Cancer vaccine, Pancreatic cancer, Cancer immunotherapy, Anti-cancer immunity

Core tip: Dendritic cell (DC)-based cancer vaccine is expected as a strategy to augment the antigen-specific anti-cancer immune response. Vaccell, a DC vaccine which was optimized to fight against a cancer, has been developed in Japan. Here, we reviewed the development and clinical effects of the “Vaccell”. We conducted large-scale retrospective observations as well as prospective clinical trials, and obtained the findings strongly suggesting that there are “Responders” that the clinical benefits are provided by the DC vaccine. We are now planning a pivotal study of the Vaccell in Japan.