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Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

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 h...

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Detalles Bibliográficos
Autores principales: Tseng, Hsiang-chi, Xiong, Wei, Badeti, Saiaditya, Yang, Yan, Ma, Minh, Liu, Ting, Ramos, Carlos A., Dotti, Gianpietro, Fritzky, Luke, Jiang, Jie-gen, Yi, Qing, Guarrera, James, Zong, Wei-Xing, Liu, Chen, Liu, Dongfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511348/
https://www.ncbi.nlm.nih.gov/pubmed/32968061
http://dx.doi.org/10.1038/s41467-020-18444-2
Descripción
Sumario: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.