Abstract LB-185: A PSMA-directed natural killer cell approach for prostate cancer immunotherapy

Abstract

Abstract Prostate Cancer (PCa) is the third leading cause of cancer mortality in men in the United States. Locally advanced or metastatic PCa is clinically managed with androgen deprivation therapy (ADT), androgen receptor antagonists, and/or taxane chemotherapy. While initially effective, patients eventually develop resistance, leading to onset of a lethal castration-resistant disease state for which no curative interventions currently exist. Cell-based immunotherapy—which is centered on infusion of modified, tumor-directed immune cells intended to drive a more potent anti-tumor response—could potentially provide a new approach to treating advanced PCa. In this study, we describe the modification of an allogeneic, immortalized human natural killer cell line, NK-92, with a chimeric antigen receptor (CAR) directed against prostate-specific membrane antigen (PSMA), a cell-surface antigen expressed by most prostate tumors. We observed that both unmodified and CAR-bearing NK-92 cells display potent cytolytic activity against the majority of PCa cell lines tested in vitro. Expression of PSMA on PCa cell lines affected the activity of CAR-modified, but not unmodified, NK-92. Combination of NK-92 immunotherapy with ADT and taxanes is also discussed, as well as ongoing in vivo preclinical modeling. Overall, CAR-modified NK-92 cells show promise as a novel immunotherapeutic agent for the treatment of PCa. Citation Format: Lucas J. Brand, Alexander B. Zaslavsky, Ganesh S. Palapattu, Karen E. Knudsen. A PSMA-directed natural killer cell approach for prostate cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-185. doi:10.1158/1538-7445.AM2017-LB-185