A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes

Kenta Furukawa, Masahiro Tanemura, Eiji Miyoshi, Hidetoshi Eguchi, Hiroaki Nagano, Katsuyoshi Matsunami, Satoshi Nagaoka, Daisaku Yamada, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Koichi Kawamoto, Kunihito Goto, Kiyomi Taniyama, Masaki Mori, Yuichiro Doki

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Objectives: Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. Methods: Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. Results: Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. Conclusions: Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.

元の言語英語
記事番号e0184901
ジャーナルPloS one
12
発行部数10
DOI
出版物ステータス出版済み - 10 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Furukawa, K., Tanemura, M., Miyoshi, E., Eguchi, H., Nagano, H., Matsunami, K., Nagaoka, S., Yamada, D., Asaoka, T., Noda, T., Wada, H., Kawamoto, K., Goto, K., Taniyama, K., Mori, M., & Doki, Y. (2017). A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes. PloS one, 12(10), [e0184901]. https://doi.org/10.1371/journal.pone.0184901