Viral vector vaccination treats orthotopic murine glioblastoma via induction of tumor-specific resident memory T cells 3360

Abstract Description The aggressiveness of glioblastoma may be due to its limited induction of anti-tumor T cells; therefore, vaccines are attractive candidates to drive tumor-specific T cells. Heterologous prime-boost vaccination with chimpanzee adenovirus (ChAdOx1) and modified vaccinia Ankara (MVA) viral vectors can generate high tumor-targeted CD8+ T cell frequencies. Therefore, we tested whether this vaccination strategy induces effective T cell responses against murine glioblastoma. We used the orthotopic syngeneic SB28.P1A glioblastoma model expressing P1A, a mouse tumor antigen. Both prophylactic and therapeutic vaccination with ChAdOx1/MVA-P1A significantly prolonged the survival of mice with SB28.P1A tumors. Tumors were enriched for P1A-specific CD8+ T cells, with 40% of CD8+ T cells P1A-specific in the tumor-bearing hemisphere, compared to 20% in the contralateral hemisphere and 5% in the blood. Strikingly, 70% of tumor-infiltrating P1A-specific CD8+ T cells were resident memory T (Trm) cells. The adoptive transfer of sorted P1A-specific Trm cells derived from vaccinated tumor-bearing mice into the brains of naïve mice sufficiently protected mice from later challenge with tumors, while P1A-specific non-Trm cells or non-P1A-specific brain-derived CD8+ T cells did not. The capability of ChAdOx1/MVA vaccination to induce antigen-specific Trms in the brain that are sufficient to protect against glioblastoma is promising for translating this therapy into clinical trials. Funding Sources Supported by NIH intramural research program ZIA BC011877 and the Ludwig Institue for Cancer Research. Topic Categories Vaccines and Immunotherapy (VAC)