Antiviral vaccines for local immunotherapy against solid tumors

Abstract

Abstract Local immunotherapy against solid tumors is considered a viable approach to stimulate the tumor immune microenvironment and anti-tumor immunity. Here, we interrogate whether preexisting anti-vaccine immunity induced by licensed subunit vaccines could be leveraged for local cancer immunotherapy in the syngeneic murine tumor models. We selected Shingrix, a VZV vaccine containing the glycoprotein E (gE) antigen and adjuvant AS01B, and Gardasil-9, a HPV vaccine containing the L1 virus-like particles and alum because of the CD4 and CD8 T cell responses they respectively induce. Intratumoral injection of Shingrix alone or with immune checkpoint blockade (CTLA-4), in prevaccinated mice delayed tumor growth and often led to complete regression. These responses were associated with the induction of CD8+ T cell responses against tumor associated antigen, to tumor immune activation and alteration of the myeloid compartment. The injection of selected MHC-II-restricted gE minimal peptide epitopes combined with polyI:C also led to durable remission suggesting a contribution of gE-specific CD4 T cells. In contrast, Gardasil-9 i.t. injection did not delay tumor growth or cause tumor rejection which suggests inefficient class I cross-presentation of native VLP in the tumor cells. However, the injection of MHC-I-restricted L1 minimal peptide epitopes led to complete and durable remissions suggesting efficient tumor control by L1-specific CD8 T cells. Our results suggest that anti-viral licensed vaccines can be leverage as a new class of immunotherapeutics for local cancer therapy and intrinsic immunogenicity properties of vaccines should be considered as these effects appeared to be vaccine specific. NIH Intramural program.