LAUSR

Metastatic castration resistant prostate cancer (mCRPC) remains a significant challenge with limited durable therapeutic responses, and innovative and effective treatment strategies are needed. Advanced mCRPC often comprises a heterogeneous population of prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC), and current targeted therapies often result in transient anti-tumor responses. Chimeric antigen receptor (CAR) T-cell therapies are being actively investigated to target mCRPC, including CARs targeting antigens that are overexpressed in PrAd. Our group has developed a CAR T cell targeting the PrAd antigen, prostate stem cell antigen (PSCA), and have an ongoing phase 1 trial at City of Hope in patients with mCRPC. However, we anticipate that targeting NEPC in addition to PrAd will be required to achieve durable anti-tumor responses in patients. Here, we have developed novel dual-targeting approaches for the simultaneous treatment of both PrAd and NEPC. Our first approach optimizes a tandem CAR T-cell approach capable of targeting distinct antigens found on both PrAd and NEPC. Additionally, we are actively developing combinations of PSCA-CAR T-cells with secretable T-cell bispecific antibodies to target NEPC antigens. Our studies encompass the in vitro and in vivo safety and efficacy of CAR T-cells engineered to co-target PrAd and NEPC for the treatment of heterogeneous mCRPC. Citation Format: Lupita S. Lopez, Nathanael Bangayan, Owen Witte, Saul J. Priceman. Development of adoptive T-cell therapies to target heterogeneity of mCRPC. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4104.