B7-H3 Targeted CAR T Cell Immunotherapy for Primary and Metastatic/Multi-focal Intrahepatic Cholangiocarcinoma

Abstract

Introduction: The lack of effective therapy for intrahepatic cholangiocarcinoma (ICC) has prompted us to develop a novel immunotherapy using T cells engineered with a chimeric antigen receptor (CAR T cells). The aim of this preliminary study is to demonstrate that B7-H3 CAR T cells are safe and effective in eradicating ICC cells orthotopically grafted in NSG (NOD scid gamma) mice and in prolonging their survival. Method: Primary tumor was established in 15 mice by orthotopic grafting of human ICC cells ICC3-GFP-Luc. Then mice were randomized into 3 groups: treatment group injected through the tail vein with B7-H3 CAR T cells (n=5), intratumorally injected (n=5) and control group (n=5), left untreated. The multi-focal/metastatic mice model was established by tail vein injection of the same cell line in 8 mice. Then mice were randomized into 2 groups: treatment group, injected through the tail vein with B7-H3 CAR T cells (n=4) and control group (n=4), left untreated. Tumor size and development of metastasis were monitored weekly by bioluminescent imaging (BLI). Results: While tail vein injected B7-H3 CAR T cells eradicated primary tumor in all the mice, the intratumorally administered B7-H3 CART cells only reduce the growth of the tumor. As far as mice with multifocal/metastatic disease is concerned, B7-H3 CART cells completely eradicate the tumor in all the mice and prolong their survival. Conclusions: B7-H3 CAR T cell therapy is effective in eradicating both primary and multi- focal disease and ICC metastases established in NSG mice and in prolonging their survival.