Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles

Personalized treatment has become a realistic option for tumor patients, accelerated by significantly reduced sequencing costs of tumor genomes and advances in vaccine formulations. The druggability of cancer neo-antigens caused by individual mutations is centered in this effort. We here use an adeno-associated virus (AAV)-based virus-like particle (VLP) platform to compose a neo-antigen-specific protein vaccine that is effective in a murine prevention and treatment setting. Furthermore, we show that CD4⁺ T cell responses that are provided by the AAV capsid are crucial for effective murine melanoma treatment. To uncover the optimal composition of a peptide vaccine we de-linked major histocompatibility complex (MHC) class II helper peptides from the capsid and formulated an efficient neo-antigen-specific vaccine, which showed the independence of CD4⁺ T cell response from tumor sequences. The findings are supported by clinical data of neo-antigen-vaccinated tumor patients. Our results punctuate on the significance of MHC class II epitopes for CD8⁺ T cell responses and suggest a future use of AAVLPs as neo-epitope vaccines in personalized cancer treatments.