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, Dongfang Liu

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

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.

Original languageEnglish (US)
Article number4810
Pages (from-to)4810
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Sep 23 2020

Keywords

  • Animals
  • Basigin/genetics
  • Carcinoma, Hepatocellular/drug therapy
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Hep G2 Cells
  • Humans
  • Immunotherapy, Adoptive/methods
  • Killer Cells, Natural
  • Liver/pathology
  • Liver Neoplasms/drug therapy
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Chimeric Antigen/drug effects
  • Xenograft Model Antitumor Assays

ASJC Scopus subject areas

  • General
  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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