Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma
Open Access
- 23 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-15
- https://doi.org/10.1038/s41467-020-18444-2
Abstract
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.Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (AI124769, AI129594, AI130197)
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (HL125018)
- Rutgers University-New Jersey Medical School Liu Laboratory Startup funding.
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