639 Phase I clinical trial of autologous gamma/delta-enriched chimeric antigen receptor (CAR)-T cells to target prostate stem cell antigen (PSCA) in patients with bone metastatic prostate cancer
Background Bone metastatic castration-resistant prostate cancer (M1b CRPC) remains a fatal disease with significant associated morbidity. PSCA is expressed in >90% of mCRPC, with limited basal expression in normal tissues. A recent clinical trial of alpha/beta CAR-T cells targeting PSCA showed feasibility and safety, with evidence of antitumor activity.1 Based on our preclinical results,2 we hypothesize that patients who receive treatment with zoledronic acid will benefit from adoptive transfer of autologous gamma/delta-enriched CAR-T cells, resulting in clinical response. We postulate that due to the bone tropism of zoledronic acid, CAR-T cells will be activated by bone-resident tumor cells through two mechanisms: 1) activation of the CAR by PSCA, and 2) activation of the endogenous gamma/delta TCR by zoledronate-induced accumulation of phosphoantigens. Methods This is a single institution phase 1 study in M1b CRPC to assess the safety of autologous gamma/delta-enriched T cells geneti
