B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer

Abstract

AbstractThe high expression across multiple solid tumor, including prostate cancer and restricted expression in normal tissues makes B7-H3 an attractive target for immunotherapy. Among various types of tumor immunotherapy, chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematological tumors. However, the potency of CAR-T cell therapy in solid tumors is still limited so far. Here, we examined the expression of B7-H3 in prostate cancer tissues and cells, and developed a second-generation CAR that specifically targets B7-H3 and CD28 as costimulatory receptor to explore its tumoricidal potential against prostate cancerin vitroandin vivo. The high expression of B7-H3 was detected on both the surface of PC3, DU145 and LNCaP cells and prostate cancer tissues. B7-H3 CAR-T cells efficiently controlled the growth of prostate cancer in an antigen-dependent mannerin vitroandin vivo. What is more, tumor cells could induce the proliferation of CAR-T cells and the release of high levels of cytokines of IFN-γ and TNF-α in vitro. These findings elucidate that B7-H3 is a potential target for prostate cancer therapy, and support the clinical development of B7-H3 specific CAR-T cells for prostate cancer.