Melanoma Vaccines

Abstract

The introduction of treatment based on immune checkpoint blockade (ICB) has revitalized immunotherapy in the treatment of melanoma and has provided a fresh impetus to examine whether melanoma vaccines may complement the results of such treatments. Although it seems likely that immune checkpoints on T cells were a major cause of failure of past trials of immunotherapy, results from ICB treatment have also pointed to the importance of neoantigens created by mutations in cellular proteins in generating the tumor rejection responses. Production of vaccines from such proteins is now seen as an important objective in vaccine design, but the individual patient-specific nature of the mutations is proving a major challenge in vaccine development. Additionally, shared antigens derived from epigenetically regulated proteins have been a long interest. Their expression in melanoma provides a further opportunity for vaccine development. The interest created from treatment benefit with ICB has generated a number of new vaccine platforms and adjuvants that may justify reexamination of previous vaccines containing common cross-reactive antigens. New insights have also been obtained into the effector T cells involved and differentiation states associated with exhausted states of T cell function. Given the excellent responses of many patients to monotherapy with ICBs, there is little need for vaccine treatment in such patients – but there remains an urgent need to identify patients who may benefit among the >50% who do not benefit durably from ICB therapy. Possible biomarkers include the mutation rate in the melanoma or identification of signal pathways in the tumor or its microenvironment that inhibit responses. Studies on these aspects are in their infancy and will need well-planned clinical trials for validation.