Background Immunotherapy based on anti CTLA-4 (αCTLA-4) and anti PD1 (αPD1) is being tested in combination with different therapeutic approaches including other immunotherapy approaches such as neoantigen cancer vaccines (NCV). Here we explored, in two cancer murine models, different therapeutic combinations of αCTLA-4 and/or αPD1 with a plasmid DNA vaccine expressing neoantigens and delivered by electroporation (EP).
Materials and Methods To evaluate the impact of NCV in the MC38 and in the CT26 tumor model three plasmid vaccines were generated with or without CD4 epitopes. Therapeutic DNA vaccines were delivered by EP in different therapeutic protocols including large tumors. Flow cytometry was utilized to measure CD8, CD4, T-reg, and B cells as well as neoantigen-specific immune responses, which were also measured by IFN-γ ELIspot.
Results Immune responses were augmented in combination with αCTLA4 but not with αPD1 in the MC38 tumor model with significantly impacting tumor growth. Similarly, neoantigen-specific T cell immune responses were observed in the CT26 tumor model where large tumors regressed in all mice treated with αCTLA-4 and NCV. In line with previous evidence, we observed an increased switched memory B cells in the spleen of mice treated with αCTLA-4 alone or in combination with NCV.
Conclusions These results support the use of NCV delivered by DNA-EP with αCTLA-4 and suggest a new combined therapy for clinical testing.
Disclosure Information F. Palombo: A. Employment (full or part-time); Significant; Neomatrix biotech. E. Salvatori: A. Employment (full or part-time); Significant; Takis biotech. L. Lione: A. Employment (full or part-time); Significant; Takis biotech. M. Compagnone: A. Employment (full or part-time); Significant; Neomatrix biotech. A. Conforti: A. Employment (full or part-time); Significant; Evvivax. L. Aurisicchio: A. Employment (full or part-time); Significant; Neomatrix biotech, Takis biotech, Evvivax.
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