2020年3月31日
GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab.
eLife
- 巻
- 9
- 号
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.7554/eLife.49392
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.
- リンク情報
- ID情報
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- DOI : 10.7554/eLife.49392
- PubMed ID : 32228854
- PubMed Central 記事ID : PMC7108862