Breaking tolerance in cancer immunotherapy: Time to ACT

The discovery of defined tumor antigens and their application in therapeutic cancer vaccines has not yet resulted in a successful therapy for cancer patients. Recent data suggest that this might be because most current clinical immunotherapeutic strategies rely on a tolerized tumor-reactive T-cell repertoire, resulting in a weak T-cell response that cannot induce tumor regression in the face of a multitude of normal and tumor-induced immunoregulatory mechanisms. New insights from animal models and clinical trials suggest a rationale for combination approaches in which the ineffective endogenous anti-tumor immune response is enhanced through a combination of adoptive cell transfer (ACT), specific vaccination and cytokine help for the reliable induction of a robust anti-tumor immune response and tumor regression.