GENERATION OF ANTIMELANOMA CYTOTOXIC T-LYMPHOCYTES FROM HEALTHY DONORS AFTER PRESENTATION OF MELANOMA-ASSOCIATED ANTIGEN-DERIVED EPITOPES BY DENDRITIC CELLS IN-VITRO

MHC class I-restricted CTLs specific for antigens expressed by maligna nt cells are an important component of immune responses against human cancer. Recently, in melanoma a number of melanocyte differentiation a ntigens have been identified as potential tumor rejection antigens. In the present study, we show that by applying peptide-loaded dendritic cells, induced by granulocyte-macrophage colony-stimulating factor and interleukin 4 from peripheral blood monocytes of healthy donors, we w ere able to elicit melanoma-associated antigen-specific CTL in vitro, We demonstrate the induction of CTLs directed against HLA-A2.1 present ed epitopes derived from tyrosinase, gp100, and Melan A/MART-1. Apart from lysis of peptide-loaded target cells, these CTLs displayed reacti vity with HLA-A2.1(+) melanoma tumor cell lines and cultured normal me lanocytes endogenously expressing the target antigen. These data indic ate that these CTLs recognize naturally processed and presented epitop es and that precursor CTLs against melanocyte differentiation antigens are present in healthy individuals, The ability to generate tumor-spe cific CTLs in vitro, using granulocyte-macrophage colony-stimulating f actor/interleukin 4-induced dendritic cells, illustrates the potential use of this type of antigen-presenting cells for vaccination protocol s in human cancer.