Annual Report 2018
Division of Cancer Immunotherapy (Kashiwa Campus)
Tetsuya Nakatsura, Yasushi Uemura, Shigehisa Kitano, Toshiaki Yoshikawa, Keigo Saito, Manami Shimomura, Kyoko Fukuda, Toshihiro Suzuki, Shoichi Mizuno, Norihiro Fujinami, Yumi Tokumitsu, Kayoko Shoda, Yukiko Kozaki, Kazuto Nosaka, Yasuhiro Shimizu, Yu Akazawa, Hiroaki Mashima, Ryoko Sasaki, Charneau Jimmy, Lin Chiahsuan, Megumi Ozaki
Introduction
Our Division aims to investigate evidencedbased 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 paper on basic data on the usefulness of cancer antigen-specific TCR gene-transferred HLA homo-iPS cells was published in Cell Stem Cell (IF: 23.290).
2) In addition, several English papers were accepted.
3) Collaborative research with companies aiming for clinical trials of neoantigen peptide vaccines is ongoing.
4) We completed a first-in-human clinical Phase I investigator-initiated trial using anti- CD4 antibody with Prof. Matsushima of the University of Tokyo and others.
5) We are preparing the first clinical application of FITC-CAR-T therapy targeting CD20 in cooperation with Prof. Tamada at Yamaguchi University.
6) We are developing iPS cell-derived CAR-T cell therapy targeting GPC3 in cooperation with Dr. Kaneko at CiRA of Kyoto University.
7) In addition, various immune cells derived from iPS cells for cancer treatment are prepared and their usefulness is studied at the basic research level.
Education
Our Division accepted and trained the following Trainees: Doctoral course of Graduate School of Medicine, Yokohama City University (1), Nagoya University Graduate School of Medicine (1), Fukui University School of Medical Sciences (1), Hiroshima University Graduate School of Biomedical and Health Sciences (1), Jikei University Graduate School of Medicine (1), Doctors course (1) and Masters course (1) of Tokyo University of Science at France (1) and Resident of NCCHE (6).
Future prospects
Immune check point blockades like anti- PD-1 antibody or anti-PD-L1 antibody and CAR-T cell therapy targeting CD19 showed high clinical effect, so the development of innovative cancer immunotherapy is required. We continue to undertake activities associated with bridging basic research and clinical application aiming at the development of novel immunotherapeutic methods.
List of papers published in 2018
Journal
1. Nakayama T, Kitano S. Immunotherapy for genitourinary tumors. Int J Urol, 26:326-333, 2019
2. Akazawa Y, Suzuki T, Yoshikawa T, Mizuno S, Nakamoto Y, Nakatsura T. Prospects for immunotherapy as a novel therapeutic strategy against hepatocellular carcinoma. World J Metaanal, 7:80-95, 2019
3. Okada M, Tada Y, Seki T, Tohyama S, Fujita J, Suzuki T, Shimomura M, Ofuji K, Kishino Y, Nakajima K, Tanosaki S, Someya S, Kanazawa H, Senju S, Nakatsura T, Fukuda K. Selective elimination of undifferentiated human pluripotent stem cells using pluripotent state-specific immunogenic antigen Glypican-3. Biochem Biophys Res Commun, 511:711-717, 2019
4. Akazawa Y, Mizuno S, Fujinami N, Suzuki T, Yoshioka Y, Ochiya T, Nakamoto Y, Nakatsura T. Usefulness of serum microRNA as a predictive marker of recurrence and prognosis in biliary tract cancer after radical surgery. Sci Rep, 9:5925, 2019
5. Akazawa Y, Nobuoka D, Takahashi M, Yoshikawa T, Shimomura M, Mizuno S, Fujiwara T, Nakamoto Y, Nakatsura T. Higher human lymphocyte antigen class I expression in early-stage cancer cells leads to high sensitivity for cytotoxic T lymphocytes. Cancer Sci, 2019
6. Shimizu Y, Suzuki T, Yoshikawa T, Endo I, Nakatsura T. Next-generation cancer immunotherapy targeting glypican-3. Front Oncol, 2019
7. Takahashi D, Kojima M, Suzuki T, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Gotohda N, Ikeda M, Nakatsura T, Ochiai A, Nagino M. Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification. Sci Rep, 8:13166, 2018
8. Kitano S, Nakayama T, Yamashita M. Biomarkers for Immune Checkpoint Inhibitors in Melanoma. Front Oncol, 8:270, 2018
9. Minagawa A, Yoshikawa T, Yasukawa M, Hotta A, Kunitomo M, Iriguchi S, Takiguchi M, Kassai Y, Imai E, Yasui Y, Kawai Y, Zhang R, Uemura Y, Miyoshi H, Nakanishi M, Watanabe A, Hayashi A, Kawana K, Fujii T, Nakatsura T, Kaneko S. Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy. Cell Stem Cell, 23:850-858. e4, 2018