Development of new immunotherapies using melanoma antigens recognized by T cells

Melanoma is a relatively immunogenic cancer and a good model to evaluate the possibilities of immunotherapies. Recent progress of molecular biology and immunology has allowed us to understand immune responses to human cancer at the molecular level. Although antigens for CD4⁺ T cells have not well been identified, various melanoma antigens recognized by CD8⁺ T cells have been identified, including tissue specific proteins (melanosomal proteins), proteins expressed in testis and a variety of cancers (Cancer-Testis antigens) and tumor specific mutated proteins. The immunological features of these antigens have been characterized for development of new immunotherapies. Based on these findings, antigen specific immunotherapies have been developed. Some of the phase I clinical trials with the identified melanoma antigens demonstrated anti-tumor effects. Immunization with the modified gp100 epitope that had high MHC binding affinity, in conjunction with incomplete freund adjuvant and high-dose IL-2, resulted in a 42 % response rate (CR+PR). Immunization with dendritic cells pulsed with tumor lysates or epitope peptides resulted in a 31 % response rate in metastatic melanoma. These immunotherapies need to be improved through modifications and better understanding of tumor escape mechanisms.