Triple synergy between vaccine and checkpoint inhibitors in a pre-clinical tumor model

Abstract

Abstract Despite advances in checkpoint inhibitor (CPI) therapy for cancer treatment, many malignancies remain resistant. Tumors deemed ‘cold’ based on lack of T cell infiltration into the stroma of the tumor show reduced potential for CPI therapy and finding the right combination to balance safety and efficacy is arduous. To study ways to circumvent these limitations, we used the preclinical mouse model of TC1 tumor cells resistant to conventional CPI therapy. The TC1 cells are transfected with oncogenes E6 and E7 of HPV16, and we designed a tumor-vaccine specific for an E7(43–77) peptide. We show the synergy between the tumor-antigen specific vaccine and the combination of two CPIs, anti-TIGIT and anti-PD-L1. The synergistic effect of the triple combination provides more protection against tumor growth than either treatment alone or any pairwise combination and significantly improves survival in a CD8+ T cell dependent manner. Combining the tumor-specific vaccine with CPIs induces tumor-specific CD8+ T cells that infiltrate the tumor in young and aged mice, although aged mice show less protection than their younger counterparts. These data show proof-of-concept for a novel combination of a vaccine designed to elicit de novo anti-tumor T cell responses that can be amplified by synergistic CPIs that lead to greater survival. Supported by Intramural NCI funding: ZIA-C-004020