Oncolytic virus-mediated GPC3 delivery overcomes antigen heterogeneity in hepatocellular carcinoma and enhances GPC3-directed immunotherapy

Background

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide and is characterized by substantial molecular and immunologic heterogeneity that contributes to therapeutic resistance and poor clinical outcomes. Glypican-3 (GPC3) is an attractive immunotherapy target in HCC; however, its heterogeneous expression limits the effectiveness of GPC3-directed approaches. ECT204, a GPC3-directed ARTEMIS® T-cell therapy, has shown improved safety compared with conventional CAR T cells but remains dependent on sufficient tumor-associated GPC3 expression. In this study, we investigated whether an oncolytic virus could be used to selectively deliver GPC3 to tumor cells to expand the applicability of GPC3-targeted immunotherapies.