@article{5fabf2a126a647289d74b02b69a32299,
title = "GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 ab",
abstract = "Current xenogeneic mouse models cannot evaluate on-target off-tumor adverse effect, hindering the development of chimeric antigen receptor (CAR) T cell therapies for solid tumors, due to limited human/mouse cross-reactivity of antibodies used in CAR and sever graft-versus-host disease induced by administered human T cells. We have evaluated safety and antitumor efficacy of CAR-T cells targeting glypican-1 (GPC1) overexpressed in various solid tumors. GPC1-specific human and murine CAR-T cells generated from our original anti-human/mouse GPC1 antibody showed strong antitumor effects in xenogeneic and syngeneic mouse models, respectively. Importantly, the murine CAR-T cells enhanced endogenous T cell responses against a non-GPC1 tumor antigen through the mechanism of antigen-spreading and showed synergistic antitumor effects with anti-PD-1 antibody without any adverse effects in syngeneic models. Our study shows the potential of GPC1 as a CAR-T cell target for solid tumors and the importance of syngeneic and xenogeneic models for evaluating their safety and efficacy.",
author = "Daiki Kato and Tomonori Yaguchi and Takashi Iwata and Yuki Katoh and Kenji Morii and Kinya Tsubota and Yoshiaki Takise and Masaki Tamiya and Haruhiko Kamada and Hiroki Akiba and Kouhei Tsumoto and Satoshi Serada and Tetsuji Naka and Ryohei Nishimura and Takayuki Nakagawa and Yutaka Kawakami",
note = "Funding Information: This work was supported by Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (26221005); the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) (14069014) and the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from Japan Agency for Medical Research and Development (AMED); a grant from Tokyo Biochemical Research Foundation; a Keio Gijuku Academic Development Funds. Ministry of Education, Culture, Grants-in-aid for Scientific Yutaka Kawakami Sports, Science, and Technology Research 262221005 Japan Agency for Medical Research Project for Development of Tomonori Yaguchi and Development Innovative Research on Cancer Therapeutic 14069014 Japan Agency for Medical Research Project for Cancer Research Yutaka Kawakami and Development And Therapeutic Evolution Tokyo Biomedical Research Research Grant Yutaka Kawakami Foundation Keio University Keio Gijuku Academic Tomonori Yaguchi Development founds. Funding Information: This work was supported by Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (26221005); the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) (14069014) and the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from Japan Agency for Medical Research and Development (AMED); a grant from Tokyo Biochemical Research Foundation; a Keio Gijuku Academic Development Funds. Publisher Copyright: {\textcopyright} Kato et al.",
year = "2020",
month = mar,
doi = "10.7554/eLife.49392",
language = "English",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}
