抄録
Human malanoma antigens and their epitopes recognized by T cells have been identified using a variety of methods. These antigens are classified as 1) melanocyte specific melanosomal proteins (MART-1, gp100, tyrosinase, TRP-1 and TRP-2), 2) proteins expressed in testis and a variety of cancers (MAGE-1, MAGE-3, BAGE and GAGE), 3) tumor specific mutated proteins (β-catenin, MUM-1 and CDK4), and 4) others (p15, GnT-V, PRAME). The HLA-A2 binding unmutated melanosomal epitopes were found to have a tendency to contain non-dominant anchor amino acids and have relatively low HLA-A2 binding affinity, suggesting that these epitopes are likely to be subdominant or cryptic self determinants. In addition, a variety of mechanisms for generating T cell epitopes on growing tumor cells have been discovered. Since a significant correlation between vitiligo development and tumor regression in the IL2 based immunotherapy was observed, autoreactive T cells specific for these self peptides may be involved in in vivo melanoma regression. Adoptive transfer of CTL recognizing these epitopes into patients resulted in tumor regression. Immunization with the MART-1, gp100 or tyrosinase peptides in conjunction with incomplete Freund adjuvant or GM-CSF also resulted in tumor regression in some patients. These observations suggest that these molecules may function as tumor rejection antigens.
Melanoma reactive CTL were efficiently induced from PBL of patients by in vitro stimulation with PBMC pulsed with these epitopes and may be useful for the adoptive transfer protocol for treatment of melanoma patients. Therefore, these identified antigens may be useful for development of new immunotherapies for melanoma patients as well as for understanding the mechanisms of T cell recognition of autologous tumor cells.
