Cancer Neoantigen Vaccines Emerge Efficacious

The past century has witnessed a paradigm shift in our understanding of the immune system's impact on tumor immunogenicity, outgrowth, and therapy. These advances come not only as a consequence of our enhanced appreciation for the mechanisms underlying immune system function but also because of new experimental technologies that made these advancements possible. Among the most impactful advances has been the development of the field of immunogenomics, which uses next-generation sequencing and predictive algorithms to rapidly identify tumor-specific mutant proteins. These mutant proteins serve as immunotherapy targets, enabling the immune system to differentiate cancer cells from normal cells. The ability to identify these so-called somatic mutation-based tumor neoantigens has led tumor immunologists to explore their efficacy in personalized cancer vaccines, first in mouse tumor models and then in human cancer patients. This review highlights the efforts leading to the discovery and use of tumor- and patient-specific neoantigens, summarizes preclinical and clinical studies that established the efficacy of tumor-specific neoantigen cancer vaccines, discusses challenges and opportunities in the therapeutic use of these vaccines in cancer patients, and summarizes current efforts to render these therapies more generalizable to a larger group of cancer patients.