Immunotherapy of Melanoma Using T-Cell-Defined Antigens

Abstract

The results obtained from the previous immunotherapies suggest that T cells play an important role in the in vivo rejection of melanoma. Using various methods, we have identified melanoma antigens recognized by autologous T cells. These antigens are classified as (1) tissue- (melanocyte-) specific melanosomal proteins, (2) cancer-testis antigens (proteins expressed in normal testis and various cancers, and (3) tumor-specific peptides derived from mutations in tumor cells, among others. A variety of mechanisms in generating T-cell epitopes on tumor cells was discovered. Using the MART-1 and gp100 antigens, new immunotherapies including immunization with Peptides, recombinant viruses, plasmid DNAs, dendritic cells pulsed with peptides as well as adoptive transfer of cytotoxic T lymphocytes (CTL) generated in vitro by stimulation with antigenic peptides, have been developed, and phase I clinical trials have been performed in the Surgery Branch of the National Cancer Institute, USA. The immunization with the gp100(209(210M)) peptide that was modified to have high HLA-A2-binding affinity, along with incomplete Freund's adjuvant and interleukin-2, resulted in 42% response rate in patients with melanoma. These immunotherapies need further improvement based on the mechanisms of tumor escape.