Immune-based therapies have demonstrated benefit in multiple clinical trials, and as we gain better knowledge of the mechanisms by which tumors avoid immune detection, new strategies can be designed to more effectively target tumor-specific antigens. Aduro BioTech, Inc. has engineered attenuated Listeria monocytogenes (Lm), to be safe for human use and to also induce potent and broad innate and adaptive immune responses including CD4 and CD8 T cells specific for tumor-associated antigens. Aduro's lead therapeutic, CRS-207, is now being evaluated in a randomized, controlled Phase 2 study in patients with metastatic pancreas cancer. Prostate cancer is the only type of cancer for which a targeted therapeutic cancer vaccine has been approved by the U.S. Food and Drug Administration (FDA). Provenge®, an autologous cellular vaccine targeting prostatic acid phosphatase (PAP) developed by the Dendreon Corporation, was approved in 2010 for patients with metastatic, castrate-resistant prostate cancer (CRPC), validating the benefits of immunotherapy and providing a new treatment for CRPC with significantly less toxicity than chemotherapy. We have developed a candidate therapeutic vaccine strain for prostate cancer, named Lm-PCaVx, in which Aduro's proprietary Lm platform has been engineered to express three antigens, PAP, NY-ESO-1 and NKX3.1. The goal is to concurrently target antigens that are expressed by tumor cells (PAP and NY-ESO-1) as well as an antigen that can be expressed by cancer stem cells (NKX3.1). PAP has been clinically validated as the target of the Provenge® vaccine; NY-ESO-1 has been shown to a tumor-associated immunological target by other vaccine approaches; and NKX3.1 is over-expressed in prostate tissue that regenerates after castration therapy. In this study, we report the construction of an Lm vaccine strain encoding these three antigens and demonstrate expression of the encoded antigens in Lm-infected antigen-presenting cells. Immunization with Lm-PCaVx induced PAP-, NY-ESO-1- and NKX3.1-specific T-cell responses in mice as well as anti-tumor-type responses in HLA-A2/HLA-DR1 transgenic mice. Together these findings support the further development of a multivalent Lm-based vaccine targeting cell-mediated immune responses against multiple tumor-associated antigens as a novel, cost-effective and rational approach for the treatment of patients with prostate cancer.

Citation Format: Douglas McNeel, Marcella Fasso, Laura Johnson, Ed Lemmens, Bill Hanson, Pete Lauer, Steven Bodovitz, Charles Drake, Dirk G. Brockstedt. Combined targeting of antigens expressed in prostate cancer and prostate stem cells using Listeria-based cancer vaccines for the treatment of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2837. doi:10.1158/1538-7445.AM2013-2837