Abstract LB-093: Vaccine based immunotherapy regimen (VBIR) for the treatment of prostate cancer

A successful cancer vaccine will activate the host immune system to induce a balanced T- and B-cell response to tumor-specific antigens that can lead to tumor regression. Effective cancer vaccines will need to overcome several challenges to accomplish this goal, such as to break tolerance to the tumor associated antigens which are mostly self antigens, induce and maintain high tumor-specific T-cell titers to keep the immune pressure on the tumor as well as to overcome the immune suppressive tumor microenvironment to keep the T-cells active at the tumor site. We have applied the lessons learned in the field to the development of a multi-component cancer immunotherapy regimen that has entered clinical testing at the beginning of 2016 for the treatment of patients with prostate cancer. The vaccine regimen consists of a chimpanzee adenovirus prime vaccination administered intramuscularly followed by DNA boost vaccinations delivered with an electroporation device and with each vaccination low dose of an anti-CTLA4 antibody is administered locally, in close proximity of the vaccine draining lymph nodes. The adenovirus and DNA express the three prostate cancer antigens PSA, PSMA and PSCA. Lastly, sutent or anti-PD-1 is added to the regimen to counter the immune suppressive tumor microenvironment by lowering myeloid derived suppressor cells (by sutent doses that are lower than the approved clinical dose) or interfering with the PD-L1/PD-1 signaling pathway (by anti-PD-1). Data will be presented in tumor-bearing mice and non human primates (NHPs) demonstrating the attributes of the heterologous prime/boost vaccine with local anti-CTLA4 that induces potent, polyclonal and functional tumor-antigen specific T- and B cell responses that are maintained at high levels for up to a year in NHPs. We could also demonstrate that low dose of sutent is highly effective at lowering MDSCs in tumors and the periphery of tumor bearing mice, resulting in significantly enhanced potency of a heterologous prime/boost cancer vaccine. Lastly, our data suggest that - in the context of active vaccination - local delivery of anti-CTLA4 is superior to systemic delivery of the immune modulator at enhancing vaccine induced T-cell responses, thereby broadening the therapeutic window of the immune modulator. Citation Format: Helen Cho, Paul Cockle, Binder Joe, Weeratna Risini, Phil White, Karin Jooss. Vaccine based immunotherapy regimen (VBIR) for the treatment of prostate cancer. [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 LB-093.