Melanoma vaccines: early progress and future promises

Melanoma vaccines aim to stimulate host immune responses against the patient's own tumor. A large number of immunotherapeutic interventions have been already studied in small-scale phase I-II trials. These approaches have been based upon presumptions of investigators, including the format in which antigen would be best administered (peptide, protein, tumor lysate, whole tumor cells or genetic material coding for the proteins of interest), the antigen delivery system and adjuvants (cytokines and dendritic cells, gene-therapy), and the route/schedule of administration. Several approaches have already demonstrated an impact on the immune system but very rarely to date upon the patients' clinical disease outcome. Recent developments in cancer immunology have helped elucidate the role of the main players in the development of host anti-tumor immune responses (including the tumor cells, different T cell subsets, and dendritic cells). These research efforts have provided the basis for the multiple vaccine trial interventions that have been proposed to boost host anti-tumor immune responses. They also have allowed the development of multiple new tools to monitor immune responses in vaccinated patients (including ELISPOT, tetramers and intracellular cytokine-release assays, as well as real-time-PCR and analysis of the T cell receptor). Although multiple cancer vaccine approaches have successfully stimulated T cell immune responses in patients with cancer, the most promising ones need to be formally tested for their ability to improve both the immunological and clinical status of the vaccinated patients in phase III randomized clinical trials.