Development of B7-H3-Directed CAR T Therapy for ICC
Arya S, Ventin M, Cattaneo G, et al. B7-H3 CAR T Cells Eradicate Intrahepatic Cholangiocarcinoma and Induce Durable Response. Journal of Experimental & Clinical Cancer Research. 2026; (doi: 10.1186/s13046-026-03723-5).
Immune checkpoint molecule B7-H3 is heavily expressed in intrahepatic cholangiocarcinoma (ICC) but less so in normal tissues and therefore may represent an ideal therapeutic target for this type of tumor, researchers say. To evaluate its potential, researchers engineered B7-H3 chimeric antigen receptor (CAR) T cells with a caspase 9 (iCas9) suicide gene-based safety switch and then evaluated the cells' anti-tumor effect against ICC. The iCas9.B7-H3 CAR T cells demonstrated substantial and lasting anti-tumor activity in vitro against multiple patient-derived ICC cell lines, while a single systemic infusion in mice achieved complete and sustained eradication of orthotopic ICC tumors in a xenograft model. The findings support additional study to assess the safety, efficacy, and translational applicability of iCas9.B7-H3 CAR T cells and to identify appropriate settings.