Isolation of melanoma antigons recognized by T-cells and development of antigen specific immunotherapy.

T cells play an important role in rejection of melanoma. We have previously identified human melanoma antigens using cDNA expression cloning with melanoma reactive T cells. These antigens represented 1) tissue specific proteins (gp100, e.g.) 2) cancer-testis antigens (NY-ESO-1, e.g.), 3) mutated peptides (β-catenin, e.g.) and others. Some of these antigens were shown to be also recognized by IgG antibodies in patient's sera, thus, they can be isolated by SEREX. Tissue specific proteins, cancer-testis antigens, proteins over-expressed in cancer cells can be isolated by various cDNA subtraction methods. Using these techniques including SAGE and GeneChip, we have isolated candidate genes for new melanoma antigens. New immunothrapy protocols including immunization with peptides, recombinant viruses, plasmid DNAs, dendritic cells pulsed with peptides as well as adoptive transfer of in vitro generated CTL by stimulation with antigenic peptides, were developed, and Phase I clinical trials have been being performed. The immunization with the gp100209(210M) peptide that was modified to have a high HLA-A2 binding affinity along with IL2 resulted in 42% response rate in patients with metastatic melanoma in the Surgery branch, National Cancer Institute. These immunotherapies require further improvement based on the isolation of new melanoma antigens with better tumor rejection ability as well as the analysis on tumor escape mechanisms. [Skin Cancer (Japan) 2000; 15: 208-216]