Cytotoxic T cell induction against human malignant melanoma cells using HLA-A24-restricted melanoma peptide cocktail.

Many human leukocyte antigen (HLA)-class I (mainly A*0201)-restricted peptide-specific cytotoxic T cells (CTLs) have been derived from peripheral blood lymphocytes (PBLs) of melanoma patients. However, few studies regarding HLA-A*2402-restricted melanoma-associated peptides have been performed, because HLA-A24 is not a common allele in Caucasians. In this study, we investigated the specific CTL-inducing activity of 5 HLA-A*2402-restricted peptides derived from gp100, tyrosinase, MAGE1, MAGE2 and MAGE3. A CTL induction culture was performed using PBLs and cultured dendritic cell (DC) pulsed with HLA-A*2402-restricted melanoma peptide cocktail. The CTLs derived from volunteers killed the A24 peptide-pulsed TISI cells and even HLA-A*2402-positive melanoma cells, but not HLA-A*0201-positive cells. IFN-gamma levels produced by the melanoma patients' CTLs were obviously low in each peptide group compared with those produced by the volunteers' CTLs, which indicated the presence of immunosuppressive factors in metastatic melanoma. These results suggested that polyvalent immunotherapy using multiple epitopes from melanoma antigens might be a better way of improving the efficacy of treatment.