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Publication : Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma.

First Author  Tseng HC Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  4810
PubMed ID  32968061 Mgi Jnum  J:298631
Mgi Id  MGI:6470292 Doi  10.1038/s41467-020-18444-2
Citation  Tseng HC, et al. (2020) Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma. Nat Commun 11(1):4810
abstractText  Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3(+)CD147(+)), but not single antigen (GPC3(-)CD147(+)) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.
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