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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2016; 22(18): 4446-4458
Published online May 14, 2016. doi: 10.3748/wjg.v22.i18.4446
Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer
Mikio Kajihara, Kazuki Takakura, Tomoya Kanai, Zensho Ito, Yoshihiro Matsumoto, Shigetaka Shimodaira, Masato Okamoto, Toshifumi Ohkusa, Shigeo Koido
Mikio Kajihara, Kazuki Takakura, Tomoya Kanai, Zensho Ito, Yoshihiro Matsumoto, Toshifumi Ohkusa, Shigeo Koido, Division of Gastroenterology and Hepatology, Department of Internal Medicine, the Jikei University School of Medicine (Kashiwa Hospital), Chiba 277-8567, Japan
Shigetaka Shimodaira, Cell Processing Center, Shinshu University Hospital, Nagano 390-8621, Japan
Masato Okamoto, Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo 108-8641, Japan
Toshifumi Ohkusa, Shigeo Koido, Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Chiba 277-8567, Japan
Author contributions: Kajihara M, Takakura K, Kanai T, Ito Z, Matsumoto Y, Shimodaira S, Okamoto M, Ohkusa T and Koido S designed the manuscript; Koido S wrote the paper; Kajihara M, Takakura K and Koido S contributed equally to this manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript.
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: Shigeo Koido, MD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, the Jikei University School of Medicine (Kashiwa Hospital), 163-1 Kashiwashita, Kashiwa, Chiba 277-8567, Japan. shigeo_koido@jikei.ac.jp
Telephone: +81-4-71641111 Fax: +81-4-71633488
Received: January 14, 2016
Peer-review started: January 16, 2016
First decision: March 21, 2016
Revised: April 1, 2016
Accepted: April 15, 2016
Article in press: April 15, 2016
Published online: May 14, 2016
Processing time: 110 Days and 22.3 Hours
Abstract

The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.

Keywords: Pancreatic cancer; Dendritic cell; Whole tumor cell; Cancer vaccine; Cytotoxic T lymphocyte

Core tip: Chemotherapy and cell-based cancer vaccines such as dendritic cell- and whole tumor cell-based cancer vaccines can synergize to result in increased efficacies in patients with pancreatic ductal adenocarcinoma (PDA). Moreover, cell-based cancer vaccines and immune checkpoint inhibitors can be used to block inhibitory ligand/receptor interactions by acting on certain cancer cells or T cells, allowing an enhancement of the antitumor immune response in specific tumors, including PDA. Therefore, the blockade of immune regulatory checkpoints combined with cell-based cancer vaccines and/or chemotherapy may be effective in inducing adaptive antitumor immunity in patients with PDA.