Abstract 2363: Combinational therapy with specific immunization plus checkpoint inhibition results in enhanced tumor regression and survival benefit

Abstract

Abstract Effective immunotherapeutic treatment of various cancers may require combinational approaches to induce specific immunity to the tumor as well as inhibition of immune check-points. We have developed a viral gene delivery platform to immunize against numerous tumor associated antigens (TAA) such as carcinoembryonic antigen (CEA), HER2/neu and HPV 16. We investigated the therapeutic benefit of the immunotherapeutics alone and in combination with check-point inhibitors such as programmed death-ligand 1 (PD-1) blockade and LAG3 blockade in murine tumor models. As single agents, immunization with the viral delivery platform encoding the TAA induced target-specific cell-mediated immunity and anti-tumor responses in the respective model. When the immunotherapies were combined with immune checkpoint blockade, an increased level of anti-tumor activity against was observed in addition to an improvement in survival. Tumor microenvironment analysis immunized mice revealed an increase in CD8+ tumor-infiltrating lymphocytes (TILs). In addition, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1+ TILs. When immunotherapy was combined with anti-PD-1 antibody, we observed CD8+ TILs at the same increased level but found that a smaller fraction of these were PD-1+. Furthermore, we observed a reduction in PD-L1 expression on tumor cells, providing a mechanism by which combination therapy favors tumor clearance and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials. Citation Format: Elizabeth Gabitzsch, Adrian Rice, Yvette Latchman, Joseph P. Balint, Frank Jones. Combinational therapy with specific immunization plus checkpoint inhibition results in enhanced tumor regression and survival benefit. [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 2363.