“Efficacy and Toxicity of CD147-CAR-NK for Hepatocellular Carcinoma Treatment”
Recent clinical trials testing cancer immunotherapies have shown promising results for the treatment of various cancers. One such therapy involves engineering immune cells to express chimeric antigen receptors (CAR), which combine tumor antigen specificity with immune cell activation in a single receptor. The adoptive transfer of these CAR-modified immune cells (especially T cells, CAR T) into patients has shown remarkable success in treating multiple refractory blood cancers. However, in order to achieve the promise of CAR-modified immune cells in treating solid tumor cancers, further advances will be required. One key challenge is identifying a safe and effective solid 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 (BSG) or extracellular matrix metalloproteinase inducer (EMMPRIN), 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 (including T and NK cells) for HCC patients. The results of these studies will also streamline the path to clinical trials of logCD147-CAR-T or -NK cells for adoptive cell therapy for the treatment of HCC. This study could be translated to the treatment of other CD147 positive solid tumor cancers as well in the future.
Hosted by Professor KiBum Lee