Vaccination with cationic liposome-encapsulated CD4 and CD8 T cell neoepitopes induces superior tumor control.

Therapeutic cancer vaccines represent a promising new development in the field of cancer immunotherapy, aiming to elicit T cell responses targeting tumor antigens. Cancer vaccines consisting of multiple tumor-specific T cell peptide epitopes require optimal formulation, as peptides by themself are poorly immunogenic. In this study, we report the development of a novel multi-epitope cationic liposomal cancer vaccine utilizing real neoepitopes and evaluated the efficacy in a murine colorectal cancer model for personalized vaccination. MHC class I and class II neoepitope peptides were successfully individually encapsulated into cationic liposomes. Upon intradermal vaccination significantly higher neoepitope-specific CD8 and CD4 T cells were induced, compared to vaccination with soluble peptides or peptides mixed with empty liposomes. Moreover, this liposomal neoepitope vaccine was highly effective in preventing MC38 tumor outgrowth and cured 60% of mice bearing a lethal tumor. In conclusion, this study shows that cationic liposomal multi-epitope peptide formulations are a promising strategy for personalized cancer immunotherapy.