While
immune checkpoint inhibition is rapidly becoming standard of care in many solid
tumors,
immune checkpoint inhibitors (ICIs) fail to induce clinical responses in many patients, presumably due to insufficient numbers of
tumor-specific T cells in the
tumor milieu. To this end, immunization protocols using viral vectors expressing
tumor-associated
antigens are being explored to induce T cell responses that synergize with ICIs. However, the optimal combination of
vaccine and immune checkpoint regimen remains undefined. Here, a dendritic cell-targeting lentiviral vector (ZVex®) expressing the endogenous murine
tyrosinase-related
protein 1 (mTRP1), or the human
tumor antigen NY-ESO-1, was explored as monotherapy or heterologous prime-boost (HPB)
vaccine regimen together with recombinant
tumor antigen in the murine
B16 melanoma model. PD1/PDL1 blockade significantly enhanced ZVex/mTRP1, but not ZVex/NY-ESO-1, induced immune responses in mice, whereas the opposite effect was observed with anti-CTLA4 antibody. Anti-
tumor efficacy of anti-PD1, but not
anti-PDL1 or anti-CTLA4, was significantly enhanced by ZVex/mTRP1 and HPB vaccination. These results suggest mechanistic differences in the effect of checkpoint blockade on
vaccine-induced immune and anti-
tumor responses against self versus non-self
tumor antigens, possibly due to tolerance and state of exhaustion of anti-
tumor T cells.