Immune checkpoint inhibitors (ICI) based on anti-CTLA-4 (αCTLA-4) and anti-PD1 (αPD1) are being tested in combination with different therapeutic approaches including other
immunotherapies such as neoantigen
cancer vaccines (NCV). Here we explored, in two
cancer murine models, different therapeutic combinations of ICI with personalized
DNA vaccines expressing neoantigens and delivered by electroporation (EP). Anti-
cancer efficacy was evaluated using
vaccines with or without CD4
epitopes. Therapeutic
DNA vaccines showed synergistic effects in different therapeutic protocols including established large
tumors. Flow cytometry (FC) was utilized to measure CD8, CD4, Treg, and switched B cells as well as neoantigen-specific immune responses, which were also measured by IFN-γ ELIspot. Immune responses were augmented in combination with αCTLA4 but not with αPD1 in the MC38
tumor-bearing mice, significantly impacting
tumor growth. Similarly, neoantigen-specific T cell immune responses were enhanced in combined treatment with αCTLA-4 in the CT26
tumor model where large
tumors regressed in all mice, while monotherapy with αCTLA-4 was less efficacious. In line with previous evidence, we observed an increased switched B cells in the spleen of mice treated with αCTLA-4 alone or in combination with NCV. These results support the use of NCV delivered by
DNA-EP with αCTLA-4 and suggest a new combined
therapy for clinical testing.