The limitations of current immune checkpoint inhibitor therapies highlight a need for improved strategies to expand tumor-reactive T cell repertoires in a way that is safe, selective and efficient. Cancer vaccines hold potential to achieve this goal, but the profound success of vaccines for infectious diseases has not yet translated to the cancer setting. Recently, however, encouraging preliminary results from phase 1 and 2 clinical trials have renewed enthusiasm and spurred the initiation of large-scale cancer vaccine trials. In this Review, we highlight insights from recent clinical trials, translational studies and preclinical models, which reveal critical factors for optimizing cancer vaccines. Key strategies include definition of improved proxies to estimate vaccine efficacy, selection of high-quality antigens-particularly neoantigens-using modular vaccine platforms with innate immunostimulatory capabilities, and a focus on early-stage cancer, as exemplified by (neo)adjuvant therapies. We discuss each of these in detail, outlining a roadmap for future cancer vaccine development.
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