CD4+ T-cell activation for immunotherapy of malignancies using Ii-Key/MHC class II epitope hybrid vaccines

► Cognate CD4+ T-cells are critical for active immunotherapy of cancer. ► CD4+ T-cells required to generate memory CD8+ cytotoxic T lymphocytes. ► Ii-Key-modified MHC class II epitopes more potently activate CD4+ T-cells. ► Ii-Key hybrids active clinically: increase specific CD4+ T-cells without adjuvant.