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oai:figshare.com:article/33920275 2026-09-18T05:27:24Z category_696 portal_316 item_type_3 month_year_09_2026

Data Sheet 1_Oncolytic virus–mediated GPC3 delivery overcomes antigen heterogeneity in hepatocellular carcinoma and enhances GPC3-directed immunotherapy.pdf Shyambabu Chaurasiya (418124) Sang-In Kim (15087808) Prakash Sah (6031358) Zhifang Zhang (47768) Yoya Vashi (8375442) Hannah Wu (6831887) Jennifer Cillis (25069993) Anthony Park (4950655) Annie Yang (160658) Yanghee Woo (5198957) Guangyang Xiong (25069996) Jingbao Liu (341670) Hongbing Zhang (181976) Pei Wang (102036) Cheng Liu (83733) Yuman Fong (266390) Genetic Immunology bite CF33 codrituzumab glypican-3 HepG2 ECT204 ARTEMIS T cells Background<p>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.</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. In vivo, combination therapy with CF33-GPC3 and ECT204, administered either intratumorally or intravenously, achieved significantly greater tumor control than either monotherapy alone. Moreover, OV-mediated GPC3 expression sensitized tumor cells to killing by GPC3-specific BiTE-redirected T cells and enhanced codrituzumab-mediated NK cell cytotoxicity.</p>Conclusions<p>These findings demonstrate that OV-mediated GPC3 delivery can overcome antigen heterogeneity in HCC and broaden the applicability of GPC3-directed immunotherapies.</p> 2026-09-18T05:27:24Z Dataset Dataset 10.3389/fimmu.2026.1894178.s001 https://figshare.com/articles/dataset/Data_Sheet_1_Oncolytic_virus_mediated_GPC3_delivery_overcomes_antigen_heterogeneity_in_hepatocellular_carcinoma_and_enhances_GPC3-directed_immunotherapy_pdf/33920275 CC BY 4.0