Data Sheet 1_Oncolytic virus–mediated GPC3 delivery overcomes antigen heterogeneity in hepatocellular carcinoma and enhances GPC3-directed immunotherapy.pdf

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.</p>Methods<p>We engineered the oncolytic vaccinia virus CF33-GPC3 to express GPC3 and evaluated its ability to sensitize GPC3-negative tumor cells to ECT204 in vitro and in vivo using GPC3-knockout HepG2 xenograft models. We also assessed the compatibility with other GPC3-targeted immunotherapies, including a bispecific T-cell engager (BiTE) and the monoclonal antibody codrituzumab.</p>Results<p>CF33-GPC3 efficiently induced surface expression of GPC3 in previously GPC3-negative tumor cells, resulting in activation of GPC3-directed ECT204 T cells and subsequent tumor cell killing.