Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Laboratory of Veterinary Surgery, Graduate school of agricultural and life sciences, The University of Tokyo, Tokyo, Japan
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Takashi Iwata
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
Yuki Katoh
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Kenji Morii
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
Yoshiaki Takise
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Masaki Tamiya
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Haruhiko Kamada
Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Tokyo, Japan
Hiroki Akiba
Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Tokyo, Japan
Kouhei Tsumoto
Center for Drug Design Research, National Institute of Biomedical Innovation, Health and Nutrition, Tokyo, Japan
Satoshi Serada
Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi, Japan
Tetsuji Naka
Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi, Japan
Ryohei Nishimura
Laboratory of Veterinary Surgery, Graduate school of agricultural and life sciences, The University of Tokyo, Tokyo, Japan
Takayuki Nakagawa
Laboratory of Veterinary Surgery, Graduate school of agricultural and life sciences, The University of Tokyo, Tokyo, Japan
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of immunology, School of Medicine, International University of Health and Welfare, Tokyo, Japan
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.
