Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma
| Autor: | Luke F Fritzky, Qing Yi, Hsiang chi Tseng, Jie gen Jiang, James V. Guarrera, Wei-Xing Zong, Ting Liu, Minh Ma, Wei Xiong, Yan Yang, Dongfang Liu, Saiaditya Badeti, Gianpietro Dotti, Carlos A. Ramos, Chen Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Cancer therapy medicine.medical_treatment General Physics and Astronomy Immunotherapy Adoptive Mice 0302 clinical medicine lcsh:Science Mice Knockout Multidisciplinary Receptors Chimeric Antigen Liver Neoplasms Hep G2 Cells Tumor antigen Killer Cells Natural Liver 030220 oncology & carcinogenesis Hepatocellular carcinoma Tumour immunology Female Immunotherapy Carcinoma Hepatocellular Science Mice Transgenic General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Immune system Antigen Cell Line Tumor medicine Carcinoma Animals Humans business.industry General Chemistry medicine.disease Xenograft Model Antitumor Assays Chimeric antigen receptor digestive system diseases Disease Models Animal 030104 developmental biology Basigin Cancer research lcsh:Q business human activities |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Chimeric antigen receptor (CAR)-based therapy for the treatment of liver cancer represents a promising therapeutic strategy. Here the authors show that CD147-targeting CAR-NK or CAR-T can induce anti-tumor activity against hepatocellular carcinoma in vitro and in vivo. |
| Databáze: | OpenAIRE |
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