Neoantigen-specific T cell help outperforms non-specific help in multi-antigen DNA vaccination against cancer.

CD4 T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC-38 colon carcinoma, encoding CD8 T cell neoantigens alone (noHELP) or in combination with either "universal" helper antigens (uniHELP) or helper neoantigens (neoHELP). Both types of helped vaccines increased the frequency of vaccine-induced CD8 T cells, and particularly uniHELP increased the fraction of KLRG1 and PD-1 effector cells.