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Major Histocompatibility Complex Class I Restricted Cytotoxic T Cells Specific for Natural Melanoma Peptides Recognize Unidentified Shared Melanoma Antigen(s)¹

Laboratory of Tumor Immunology [M. A. I., S. M., G. C., M. B., C. R., M. P. P.], Gene Therapy Program [V. R., C. T.], Universita Vita-Salute [C. R.], and Cancer Immunotherapy and Gene Therapy Program [M. A. I., S. M., V. R., G. C., M. B., C. R., C. T., M. P. P.], Scientific Institute H. San Raffaele, 20132 Milan, Italy

CTLs were generated in vitro from two healthy donors and one melanoma patient by stimulation of CD8⁺ T cells with autologous dendritic cells pulsed with natural melanoma peptides (NMPs), obtained by acid treatment of HLA-matched melanoma cells. CTLs showed MHC class I-restricted melanoma-specific cytolytic activity. Importantly, CTLs from the patient, induced with NMPs obtained from an allogeneic HLA-A-matched melanoma, killed the autologous tumor. COS-7 cells cotransfected with the cDNA of 13 melanoma antigens and the HLA-A1-restricting allele did not induce cytokines release from NMP-specific CTLs, suggesting that they recognize unidentified shared melanoma antigens and that they may be valuable for identification of new tumor antigens. These results strongly support the use of autologous and/or allogeneic NMP-pulsed dendritic cells as cancer vaccines in patients whose neoplasms do not express or have lost expression of known tumor antigens.

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