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.