Annual Report 2020
Division of Cancer Immunotherapy
Tetsuya Nakatsura, Yasushi Uemura, Toshiaki Yoshikawa, Keigo Saito, Manami Shimomura, Kyoko Fukuda, Arnaud Couzinet, Norihiro Fujinami, Shoichi Mizuno, Kayoko Shoda, Yukiko Kozaki, Karin Iwasa, Kumiko Yamashima, Kazumasa Takenouchi, Rieko Oki, Daiki Ikarashi, Masateru Yamamoto, Ryoko Sasaki, Charneau Jimmy, Lin Chiahsuan, Hiroki Kinoshita, Toshihiro Suzuki, Shigehisa Kitano, Megumi Ozaki
Introduction
Our division aims to investigate evidenced-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 the suppression of recurrence or for cancer prevention.
Research activities
1) Public research funds and joint research funds were constantly obtained, and joint research with companies and academia increased.
2) Research aiming at clinical trials of personalized 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 COVID-19 vaccine and cell-mediated immunity test method are being 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) Phase I clinical trial of FITC-CAR-T therapy targeting CD20 is being conducted in cooperation with Prof. Tamada at Yamaguchi University.
8) We are preparing to start Phase I clinical trial of iPS cell-derived CAR-ILC/NK cell therapy targeting GPC3 in cooperation with Dr. Kaneko at 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 in France and Taiwan, and residents and senior residents of NCCHE.
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, so the development of innovative cancer immunotherapy is required. We continue to undertake activities associated with bridging basic research and clinical application aiming at developing novel immunotherapeutic methods.
List of papers published in 2020
Journal
1. Hayashi T, Kohsaka S, Takamochi K, Kishikawa S, Ikarashi D, Sano K, Hara K, Onagi H, Suehara Y, Takahashi F, Saito T, Nakatsura T, Kitano S, Suzuki K, Yao T. Histological characteristics of lung adenocarcinoma with uncommon actionable alterations: special emphasis on MET exon 14 skipping alterations. Histopathology, 78:987-999, 2021
2. Morisue R, Kojima M, Suzuki T, Nakatsura T, Ojima H, Watanabe R, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Ishii G, Gotohda N, Fujiwara T, Ochiai A. Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses. Int J Cancer, 149:546-560, 2021
3. Su Y, Yamazaki S, Morisue R, Suzuki J, Yoshikawa T, Nakatsura T, Tsuboi M, Ochiai A, Ishii G. Tumor-Infiltrating T Cells Concurrently Overexpress CD200R with Immune Checkpoints PD-1, CTLA-4, and TIM-3 in Non-Small-Cell Lung Cancer. Pathobiology, 88:218-227, 2021
4. Mizuhashi S, Kubo Y, Fukushima S, Kanemaru H, Nakahara S, Miyasita A, Ishibashi T, Kuriyama H, Kimura T, Masuguchi S, Zhang R, Iwama T, Nakatsura T, Uemura Y, Senju S, Ihn H. Immune cell therapy against disseminated melanoma by utilizing induced pluripotent stem cell-derived myeloid cell lines producing interferon-beta or interleukin-15/interleukin-15 receptor alpha. J Dermatol Sci, 102:133-136, 2021
5. Mashima H, Zhang R, Kobayashi T, Tsukamoto H, Liu T, Iwama T, Hagiya Y, Yamamoto M, Fukushima S, Okada S, Idiris A, Kaneko S, Nakatsura T, Ohdan H, Uemura Y. Improved safety of induced pluripotent stem cell-derived antigen-presenting cell-based cancer immunotherapy. Mol Ther Methods Clin Dev, 21:171-179, 2021
6. Kuriyama H, Fukushima S, Kimura T, Kanemaru H, Miyashita A, Okada E, Kubo Y, Nakahara S, Tokuzumi A, Nishimura Y, Kajihara I, Makino K, Aoi J, Masuguchi S, Tsukamoto H, Inozume T, Zhang R, Nakatsura T, Uemura Y, Senju S, Ihn H. Immunotherapy with 4-1BBL-Expressing iPS Cell-Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma. Int J Mol Sci, 22:2021
7. Aoki H, Ueha S, Shichino S, Ogiwara H, Shitara K, Shimomura M, Suzuki T, Nakatsura T, Yamashita M, Kitano S, Kuroda S, Wakabayashi M, Kurachi M, Ito S, Doi T, Matsushima K. Transient Depletion of CD4+ Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer. Cancer Immunol Res, 2021
8. Ukai M, Yokoi A, Yoshida K, Suzuki S, Shibata K, Kikkawa F, Nakatsura T, Kajiyama H. Extracellular miRNAs as Predictive Biomarkers for Glypican-3-Derived Peptide Vaccine Therapy Response in Ovarian Clear Cell Carcinoma. Cancers (Basel), 13:2021
9. Kim Y, Kobayashi E, Suehara Y, Ito A, Kubota D, Tanzawa Y, Endo M, Nakatani F, Nakatsura T, Kawai A, Kaneko K, Kitano S. Immunological status of peripheral blood is associated with prognosis in patients with bone and soft-tissue sarcoma. Oncol Lett, 21:212, 2021
10. Iriguchi S, Yasui Y, Kawai Y, Arima S, Kunitomo M, Sato T, Ueda T, Minagawa A, Mishima Y, Yanagawa N, Baba Y, Miyake Y, Nakayama K, Takiguchi M, Shinohara T, Nakatsura T, Yasukawa M, Kassai Y, Hayashi A, Kaneko S. A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy. Nat Commun, 12:430, 2021
11. Oka M, Xu L, Suzuki T, Yoshikawa T, Sakamoto H, Uemura H, Yoshizawa AC, Suzuki Y, Nakatsura T, Ishihama Y, Suzuki A, Seki M. Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer. Genome Biol, 22:9, 2021
12. Nakajima H, Nakatsura T. Towards the era of immune checkpoint inhibitors and personalized cancer immunotherapy. Immunol Med, 44:10-15, 2021
13. Daiko H, Marafioti T, Fujiwara T, Shirakawa Y, Nakatsura T, Kato K, Puccio I, Hikichi T, Yoshimura S, Nakagawa T, Furukawa M, Stoeber K, Nagira M, Ide N, Kojima T. Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients. Cancer Immunol Immunother, 69:2247-2257, 2020
14. Ikarashi D, Kitano S, Ishida K, Nakatsura T, Shimodate H, Tsuyukubo T, Tamura D, Kato R, Sugai T, Obara W. Complete Pathological Response to Neoadjuvant Pembrolizumab in a Patient With Chemoresistant Upper Urinary Tract Urothelial Carcinoma: A Case Report. Front Oncol, 10:564714, 2020
15. Mashima H, Zhang R, Kobayashi T, Hagiya Y, Tsukamoto H, Liu T, Iwama T, Yamamoto M, Lin C, Nakatsuka R, Mishima Y, Watanabe N, Yamada T, Senju S, Kaneko S, Idiris A, Nakatsura T, Ohdan H, Uemura Y. Generation of GM-CSF-producing antigen-presenting cells that induce a cytotoxic T cell-mediated antitumor response. Oncoimmunology, 9:1814620, 2020
16. Taniguchi M, Mizuno S, Yoshikawa T, Fujinami N, Sugimoto M, Kobayashi S, Takahashi S, Konishi M, Gotohda N, Nakatsura T. Peptide vaccine as an adjuvant therapy for glypican-3-positive hepatocellular carcinoma induces peptide-specific CTLs and improves long prognosis. Cancer Sci, 111:2747-2759, 2020
17. Akazawa Y, Saito Y, Yoshikawa T, Saito K, Nosaka K, Shimomura M, Mizuno S, Nakamoto Y, Nakatsura T. Efficacy of immunotherapy targeting the neoantigen derived from epidermal growth factor receptor T790M/C797S mutation in non-small cell lung cancer. Cancer Sci, 111:2736-2746, 2020
18. Ueda T, Kumagai A, Iriguchi S, Yasui Y, Miyasaka T, Nakagoshi K, Nakane K, Saito K, Takahashi M, Sasaki A, Yoshida S, Takasu N, Seno H, Uemura Y, Tamada K, Nakatsura T, Kaneko S. Non-clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell-derived anti-glypican-3 chimeric antigen receptor-expressing natural killer/innate lymphoid cells. Cancer Sci, 111:1478-1490, 2020
19. Miura M, Fujinami N, Shimizu Y, Mizuno S, Saito K, Suzuki T, Konishi M, Takahashi S, Gotohda N, Suto K, Yoshida T, Nakatsura T. Usefulness of plasma full-length glypican-3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery. Oncol Lett, 19:2657-2666, 2020