2020年3月
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
-
- DOI
- https://doi.org/10.7554/eLife.49392
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/32228854
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108862
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85082731533&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85082731533&origin=inward
- ID情報
-
- DOI : 10.7554/eLife.49392
- eISSN : 2050-084X
- PubMed ID : 32228854
- PubMed Central 記事ID : PMC7108862
- SCOPUS ID : 85082731533