Interrogating the Safety and Efficacy of a Novel STEAP1 Chimeric Antigen Receptor T-Cell Therapy in Prostate Cancer

In this reporting period, we profiled the spatial expression of human STEAP1 in our novel humanized STEAP1 knock-in (hSTEAP1-KI) mice. We identified human STEAP1 expression in the prostate and adrenal gland of male hSTEAP1-KI mice and further localized expression to luminal prostate epithelial cells and adrenal cortical cells. The hSTEAP1-KI mouse model was engrafted with the RM9 mouse prostate cancer cell line engineered to express human STEAP1 and was treated with mouse STEAP1 CAR T cells. These studies demonstrated antitumor activity andpreliminary safety of STEAP1 CAR T cell therapy as no premature deaths, weight loss, or on-target off-tumor toxicities specific to STEAP1 CAR T cells were appreciated. We did observe antigen escape as a mechanism of treatment resistance. To address this, we combined STEAP1 CAR T cell therapy with collagen binding domain (CBD)-IL-12 fusion cytokine therapy to demonstrate enhanced therapeutic efficacy by broadening the antitumor response and inducing epitope spreading.