Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

Hsiang-chi Tseng, Wei Xiong, Saiaditya Badeti, Yan Yang, Minh Ma, Ting Liu, Carlos A. Ramos, Gianpietro Dotti, Luke Fritzky, Jie-gen Jiang, Qing Yi, James Guarrera, Wei-Xing Zong, Chen Liu and Dongfang Liu ()
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Hsiang-chi Tseng: Rutgers University-New Jersey Medical School
Wei Xiong: Rutgers University-New Jersey Medical School
Saiaditya Badeti: Rutgers University-New Jersey Medical School
Yan Yang: Rutgers University-New Jersey Medical School
Minh Ma: Rutgers University-New Jersey Medical School
Ting Liu: Rutgers University-New Jersey Medical School
Carlos A. Ramos: Baylor College of Medicine, One Baylor Plaza
Gianpietro Dotti: University of North Carolina
Luke Fritzky: Rutgers University-New Jersey Medical School
Jie-gen Jiang: Rutgers University-New Jersey Medical School
Qing Yi: Houston Methodist Research Institute
James Guarrera: New Jersey Medical School, Rutgers-The State University of New Jersey
Wei-Xing Zong: Rutgers-The State University of New Jersey
Chen Liu: Rutgers University-New Jersey Medical School
Dongfang Liu: Rutgers University-New Jersey Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-18444-2

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