Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines.

Somatic mutations binding to the patient's MHC and recognized by autologous T cells (neoepitopes) are ideal cancer vaccine targets. They combine a favorable safety profile due to a lack of expression in healthy tissues with a high likelihood of immunogenicity, as T cells recognizing neoepitopes are not shaped by central immune tolerance. Proteins mutated in cancer (neoantigens) shared by patients have been explored as vaccine targets for many years. Shared ("public") mutations, however, are rare, as the vast majority of cancer mutations in a given tumor are unique for the individual patient. Recently, the novel concept of truly individualized cancer vaccination emerged, which exploits the vast source of patient-specific "private" mutations. Concurrence of scientific advances and technological breakthroughs enables the rapid, cost-efficient, and comprehensive mapping of the "mutanome," which is the entirety of somatic mutations in an individual tumor, and the rational selection of neoepitopes. How to transform tumor mutanome data to actionable knowledge for tailoring individualized vaccines "on demand" has become a novel research field with paradigm-shifting potential. This review gives an overview with particular focus on the clinical development of such vaccines. ©2016 American Association for Cancer Research.