Active Immunotherapy With Prostvac (R) Demonstrates Potent Antitumor Efficacy In A Mouse Model Of Prostate Cancer.

BN ImmunoTherapeutics (BNIT) specializes in developing novel active immunotherapies for cancer. These therapies use recombinant poxviruses engineered to express tumor-associated antigens (TAAs), with the intent of generating effective immune responses against the patients9 cancer. PROSTVAC® is a candidate product for the treatment of prostate cancer for which a global Phase III clinical trial (PROSPECT) was recently initiated. This product is composed of two different viral vectors derived from a recombinant vaccinia virus (PROSTVAC™-V) and a recombinant fowlpox virus (PROSTVAC™-F). Both vectors contain transgenes encoding prostate-specific antigen (PSA) and a triad of costimulatory molecules (B7-1, ICAM-1, and LFA-3), designated as TRICOM™. Patients are immunized using a prime-boost strategy consisting of an initial treatment with PROSTVAC™-V followed by repeated boosting with PROSTVAC™-F to maximize the immune responses against the PSA tumor-antigen. Here we show preclinical data characterizing PROSTVAC® activity in mice. Treatment with either PROSTVAC™-V or PROSTVAC™-F induced PSA-specific antibody and T cell responses; however, PSA-specific responses were further increased by the prime/boost strategy, particularly with respect to the frequency of responding CD8 T cells. These CD8 T cells produced IFN-gamma and degranulated in an antigen-specific manner. Furthermore, PROSTVAC® treatment resulted in strong efficacy in a mouse model of prostate cancer. In this model, treatment with PROSTVAC resulted in anti-tumor efficacy accompanied by a Th1-biased response against PSA. In contrast, growth of tumors in control mice induced only non-protective PSA-specific responses with strong Th2 bias. Overall, these animal studies help define the activity and mechanism of action of PROSTVAC® which is currently being evaluated in the clinic. R.B. Rountree and S.J. Mandl contributed equally to this work. Citation Format: Ryan B. Rountree, Stefanie J. Mandl, Joseph Cote, Tracy dela Cruz, Thierry Giffon, Evan Gordon, Susan P. Foy, John R. Lombardo, Erica Trent, Reiner Laus, Alain Delcayre. Active immunotherapy with PROSTVAC ® demonstrates potent antitumor efficacy in a mouse model of prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A21.