Anti-tumor effects of GPC3 CAR-iNKT cells in murine models of hepatocellular carcinoma.

Glypican-3 (GPC3) has been identified as a compelling target for immunotherapy against hepatocellular carcinoma (HCC), owing to its selective expression on tumor cells. Chimeric antigen receptor invariant natural killer T (CAR-iNKT) cells have emerged as an innovative alternative to CAR-T cells, offering potential advantages for allogeneic applications in cellular therapy. In this study, we engineered GPC3-targeted CAR-iNKT cells and demonstrated their specific cytotoxic activity against GPC3-positive HCC cells in vitro. Using a murine HCC model, we further validated that GPC3 CAR-iNKT cells effectively suppressed tumor progression and enhanced survival outcomes. Pharmacokinetic studies showed favorable persistence of CAR-iNKT cells in vivo, with low off-target toxicity observed in critical organs. Collectively, these preclinical findings suggest that GPC3 CAR-iNKT cells may provide a safe and effective therapeutic option for HCC, warranting further investigation in clinical trials.