Combination of local radiotherapy with an RNA-LPX vaccine that encodes CD4+ T cell-recognized neoantigens resulted in a poly-antigenic, potent CD8+ T cell response and memory that rejected CT26 tumor re-challenge, had higher number of polyfunctional IFN-γ+ CD4+ TH1 cells specific for the immunodominant CD4 neoantigen ME1, elevated numbers of activated gp70-specific CD8+ T cells, and lower PD-1/LAG-3 expression. The gene discussed is CD8A; the disease is neoplasm.