Annual Report 2017
Division of Cancer Immunotherapy (Kashiwa Campus / Tsukiji Campus)
Tetsuya Nakatsura, Yasushi Uemura, Shigehisa Kitano, Toshiaki Yoshikawa, Keigo Saito, Manami Shimomura, Kyoko Fukuda, Toshihiro Suzuki, Nobuhiro Tsuchiya , Tatsuaki Iwama, Norihiro Fujinami, Shoichi Mizuno, Yumi Tokumitsu, Kayoko Shoda, Yukiko Kozaki, Kazuto Nosaka, Yasuhiro Shimizu, Yu Akazawa, Megumi Ozaki
Introduction
The Division of Cancer Immunotherapy aims to investigate evidence-based cancer immunotherapy, repeating basic research and translational research. This division is focused on developing not only more effective immunotherapies but also immunological methods for suppression of recurrence or for cancer prevention.
Research activities
1) A first-in-human clinical Phase I investigator initiated trial using original peptide vaccine derived from HSP105 for patients with advanced esophageal / colorectal cancer was conducted and completed.
2) An English paper on clinical Phase I trials of GPC3 peptide vaccine for childhood cancer was published.
3) An English paper on clinical trials to evaluate the immunological effectiveness of GPC3 peptide vaccine for advanced hepatocellular carcinoma was published.
4) An English paper on the review of cancer immunotherapy targeting GPC3 and neoantigen was published.
5) Collaborative research with companies aiming for clinical trials of neoantigen peptide vaccines began.
6) We conducted first-in-human clinical Phase I investigator initiated trial using anti-CD4 antibody with Prof. Matsushima of the University of Tokyo and others.
7) We are preparing the first clinical application of FITC-CAR-T therapy targeting CD20 in cooperation with Prof. Tamada at Yamaguchi University.
8) We are developing iPS cell-derived CAR-T cell therapy targeting GPC3 in cooperation with Dr. Kaneko at CiRA of Kyoto University.
9) For iPS cell-derived TCR-T cell therapy targeting GPC3, collaborative research with Kyoto University and Takeda Pharmaceutical Co., Ltd. is ongoing.
10) In addition, various immune cells derived from iPS cells for cancer treatment are prepared and their usefulness is studied at the basic research level.
Clinical trials
We completed a phase I study of HSP105 peptide vaccine for patients with esophageal cancer and colorectal cancer.
Education
Our division accepted and trained the following trainees: Doctoral course of Graduate School of Medicine, Yokohama City University (2); Nagoya University Graduate School of Medicine (1); University of Fukui School of Medical Sciences (1); Master's course of Aix-Marseille University at France (1); and surgical resident of the National Cancer Center Hospital East (NCCHE) (3).
Future prospects
Immune checkpoint blockades like anti-PD-1 antibody or anti-PD-L1 antibody, and CAR-T cell therapy targeting CD19 showed high clinical effect, therefore the development of innovative cancer immunotherapy is required. We continue to practice activities of bridging basic research and clinical applications aiming at the development of novel immunotherapeutic methods.
List of papers published in January 2017 - March 2018
Journal
1. Tsuchiya N, Yoshikawa T, Fujinami N, Saito K, Mizuno S, Sawada Y, Endo I, Nakatsura T. Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma. Oncoimmunology, 6:e1346764, 2017
2. Tsuchiya N, Hosono A, Yoshikawa T, Shoda K, Nosaka K, Shimomura M, Hara J, Nitani C, Manabe A, Yoshihara H, Hosoya Y, Kaneda H, Kinoshita Y, Kohashi K, Yoshimura K, Fujinami N, Saito K, Mizuno S, Nakatsura T. Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors. Oncoimmunology, 7:e1377872, 2017
3. Liu H, Chen L, Liu J, Meng H, Zhang R, Ma L, Wu L, Yu S, Shi F, Li Y, Zhang L, Wang L, Feng S, Zhang Q, Peng Y, Wu Q, Liu C, Chang X, Yang L, Uemura Y, Yu X, Liu T. Co-delivery of tumor-derived exosomes with alpha-galactosylceramide on dendritic cell-based immunotherapy for glioblastoma. Cancer Lett, 411:182-190, 2017
4. Ofuji K, Saito K, Suzuki S, Shimomura M, Shirakawa H, Nobuoka D, Sawada Y, Yoshimura M, Tsuchiya N, Takahashi M, Yoshikawa T, Tada Y, Konishi M, Takahashi S, Gotohda N, Nakamoto Y, Nakatsura T. Perioperative plasma glypican-3 level may enable prediction of the risk of recurrence after surgery in patients with stage I hepatocellular carcinoma. Oncotarget, 8:37835-37844, 2017
5. Shimizu Y, Suzuki T, Yoshikawa T, Tsuchiya N, Sawada Y, Endo I, Nakatsura T. Cancer immunotherapy-targeted glypican-3 or neoantigens. Cancer Sci, 109:531-541, 2018
6. Tomuleasa C, Fuji S, Berce C, Onaciu A, Chira S, Petrushev B, Micu WT, Moisoiu V, Osan C, Constantinescu C, Pasca S, Jurj A, Pop L, Berindan-Neagoe I, Dima D, Kitano S. Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia. Front Immunol, 9:239, 2018
7. Kawachi A, Yoshida H, Kitano S, Ino Y, Kato T, Hiraoka N. Tumor-associated CD204+ M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma. Cancer Sci, 109:863-870, 2018