Cancer vaccines in the era of checkpoint blockade: the magic is in the adjuvant

•Cancer vaccines can synergize with anti-CTLA-4/PD-1 checkpoint blockade therapy.•Effective vaccine adjuvants deliver multiple synergistic signals to the immune system.•Effective preclinical vaccine adjuvants are rarely translated to the clinic.•Combination adjuvants are likely to unlock greater therapeutic efficacy of cancer vaccines.

While T cell checkpoint blockade therapy of various cancers yields impressive clinical benefits, most patients are not cured. This is thought to result from insufficient spontaneous tumor-specific T cell responses, a situation that could be remedied with cancer-specific vaccination. Much work is underway to identify cancer-specific antigens, leaving open the question of how to formulate these antigens in a manner that provokes potent cancer-specific T cell responses. In this review I discuss paradigms guiding adjuvant development, and consider what may constitutes a clinically relevant T cell response. I also suggest that adjuvants providing multiple non-redundant signals may be the next frontier in the development of cancer vaccines that provide true clinical benefit when combined with T cell checkpoint blockade.