ABSTRACT
Summary Melanoma is a relatively immunogenic cancer and responds to various immunotherapies. Clinical and immunological observations obtained from patients received various immunotherapy protocols indicate that CD8 T cells are involved in in vivo tumor rejection, and melanoma reactive CD8 T cells with various antigen specificity were generated from the patients. Using these T cells and cDNA expression cloning techniques, various melanoma antigens recognized by CD8 T cells were identified. The representative antigens are tissue (melanocyte)-specific proteins (e.g. gp100), cancer-testis antigens that are preferentially expressed in various cancers and normal testis (e.g. MAGE) and tumor specific mutated peptides (e.g. -catenin) and others. These antigens can also be isolated using various methods including cDNA expression cloning with patients’ sera (SEREX) and cDNA subtraction with RDA, SAGE, DNAChip and EST databases. Analysis of T-cell epitopes in these antigens revealed the mechanisms for generation of tumor antigens recognized by CD8 T cells and the nature of anti-tumor T-cell responses. The identification of antigenic peptides also allowed us to analyze anti-tumor T-cell responses in more detail particularly using the histocompatibility leukocyte antigen (HLA) tetramer technique as well as to develop new types of immunotherapy. In addition, modified antigens with higher immunogenicity can be generated for effective immunotherapy. These results obtained from the melanoma research may be useful for development of immunotherapy for patients with various cancers.
