Annual Report 2022
Division of Cancer Immunotherapy
Tetsuya Nakatsura, Yasushi Uemura, Manami Shimomura, Kyoko Fukuda, Nobuo Tsukamoto, Norihiro Fujinami, Arnaud Couzinet, Kazumasa Takenouchi, Kazunobu Onuki, Kayoko Shoda, Yukiko Kozaki, Karin Iwasa, Rieko Oki, Hiroki Kinoshita, Rei Tachinooka, Toshihiro Suzuki, Shoichi Mizuno, Megumi Ozaki
Introduction
Our division investigates evidence-based cancer immunotherapy by repeating basic and translational researches. This division is focused on developing not only more effective immunotherapies but also immunological methods to suppress recurrence or to prevent cancer.
The Team and What We Do
- Non-clinical basic research aimed at FIH clinical trial of new TCR gene introduction/CAR gene introduction T-cell therapy
- Non-clinical basic research aimed at FIH clinical trial of various iPS cell-derived immune cell therapies
- Development of a diagnostic method for predicting cancer onset and recurrence using blood samples
- Basic research aimed at the clinical application of personalized T cell therapy
- Basic research aimed at developing vaccines to prevent cancer recurrence
- Associated research using patient specimens for various physician-initiated clinical trials
Research Activities and Clinical Trials
1) Public research funds and joint research funds were constantly obtained, and many types of joint researches with companies and academia were conducted.
2) Research aimed at clinical trials of cancer vaccines is ongoing.
3) Personalized T cell therapy is being developed.
4) Research on circulating tumor cells in the blood is being conducted.
5) Research and development of a cell-mediated immunity test method for the COVID-19 vaccine were conducted.
6) Various immune cells derived from iPS cells for cancer treatment are prepared, and their usefulness is studied at the basic research level.
7) A phase I clinical trial of FITC-CAR-T therapy targeting CD20 was conducted in cooperation with Prof. Tamada at Yamaguchi University.
8) A phase I clinical trial of iPS cell-derived CAR-ILC/NK cell therapy targeting GPC3 is being conducted in cooperation with Dr. Kaneko at the CiRA of Kyoto University.
9) We are engaged in development research aimed at clinical trials of novel CAR-T cell therapies.
Education
Our division accepted and trained the following trainees: students of doctoral course of the Graduate School of Medicine and Medical Doctors, students of doctors course and masters course of Tokyo University of Science, and residents and senior residents of the NCCHE. A doctoral course graduate was produced.
Future Prospects
Immune checkpoint blockades, such as anti-PD-1 antibody or anti-PD-L1 antibody, and CAR-T cell therapy targeting CD19 showed high clinical effects; therefore, the development of innovative cancer immunotherapy is required. We continue to undertake activities associated with bridging basic research and clinical application, aiming to develop novel immunotherapeutic methods.
List of papers published in 2022
Journal
1. Ueda T, Shiina S, Iriguchi S, Terakura S, Kawai Y, Kabai R, Sakamoto S, Watanabe A, Ohara K, Wang B, Xu H, Minagawa A, Hotta A, Woltjen K, Uemura Y, Kodama Y, Seno H, Nakatsura T, Tamada K, Kaneko S. Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells. Nature biomedical engineering, 7:24-37, 2023
2. Fukushima S, Miyashita A, Kuriyama H, Kimura T, Mizuhashi S, Kubo Y, Nakahara S, Kanemaru H, Tsuchiya N, Mashima H, Zhang R, Uemura Y. Future prospects for cancer immunotherapy using induced pluripotent stem cell-derived dendritic cells or macrophages. Experimental dermatology, 32:290-296, 2023
3. Thi Viet Ha M, Hamana H, Shitaoka K, Hayee A, Kobayashi E, Yoshikawa T, Nakatsura T, Saikawa R, Sato E, Osawa M, Hitoshi Y, Son Dang T, Ozawa T, Kishi H. Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers. Cancer science, 114:2254-2264, 2023
4. Morishita Y, Takenouchi K, Sakashita S, Matsuura K, Hayashi R, Nakatsura T. Immunohistochemical Analysis of Common Cancer Antigens in Head and Neck Squamous Cell Carcinoma. Anticancer research, 42:5751-5761, 2022
5. Yoshioka Y, Shimomura M, Saito K, Ishii H, Doki Y, Eguchi H, Nakatsura T, Itoi T, Kuroda M, Mori M, Ochiya T. Circulating cancer-associated extracellular vesicles as early detection and recurrence biomarkers for pancreatic cancer. Cancer science, 113:3498-3509, 2022
6. Onagi H, Horimoto Y, Sakaguchi A, Ikarashi D, Yanagisawa N, Nakayama T, Nakatsura T, Ishizuka Y, Sasaki R, Watanabe J, Saito M, Saeki H, Hayashi T, Arakawa A, Yao T, Kitano S. High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs. Breast cancer research, 24:67, 2022