Abstract 2067: Attacking prostate cancer with a prodrug-doped cellular Trojan horse

Abstract

Abstract Prostate cancer is the second leading cause of cancer-related deaths in American men. Despite considerable advances in prostate cancer research, there is a major need for a systemic delivery platform that efficiently targets anti-cancer drugs to sites of disseminated prostate cancer while minimizing host toxicity. Human mesenchymal stem cells (MSCs) are excellent candidates for cell-based drug delivery since they display tropism towards cancer sites and clinical studies have demonstrated that hundreds of millions of allogeneic human MSCs can be safely administered intravenously without adverse effects in a variety of pathological settings. Furthermore, we have previously documented that MSCs can be detected in radical prostatectomy tissue from men with prostate cancer. In this proof-of-concept study, human MSCs were loaded with poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) encapsulating the macromolecule G114, a thapsigargin-based prostate specific antigen (PSA)-activated prodrug. G114-loaded MPs were successfully internalized by MSCs without impacting MSC viability, followed by sustained release of G114 as an intact prodrug from loaded cells. Moreover, G114 released from G114 MP-loaded MSCs is selectively toxic to the PSA-secreting prostate cancer cell line, LNCaP. Finally, G114 MP-loaded MSCs inhibited tumor growth when co-inoculated with CWR22 prostate cancer xenografts, suggesting that cell-based delivery of G114 does not compromise potency of the prodrug in vitro or in vivo. We envision that this MSC-based platform may be developed into an effective, systemic ‘Trojan Horse’ therapy for the targeted delivery of therapeutic agents to sites of metastatic prostate cancer. Citation Format: Nathaniel Brennen, Oren Levy, Edward Han, David Marc Rosen, Juliet Musabeyezu, Helia Safaee, Sudhir Ranganath, Jessica Ngai, Martina Heinelt, Sandrine Billett, Neil Bhowmick, Samuel Denmeade, Jeffrey Karp, John Isaacs. Attacking prostate cancer with a prodrug-doped cellular Trojan horse. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2067.