Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1.

摘要: MART-1 is an Ag expressed on melanomas and melanocytes, recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. In present study we have analyzed 10 potential 9-mer epitopes containing HLA-A2.1 binding motifs for their ability to induce melanoma-specific T cell lines. Antimelanoma CTL could be generated only with MART-1(27-35) peptide, which has been previously shown a TIL. Anti-MART-1(35-43)-specific also induced, but these cells did not recognize cells. MART-1(27-35)-specific effectively total 11 12 PBL 3 TIL derived HLA-A2+ patients, as well 2 4 healthy donors in vitro stimulation autologous PBMC pulsed synthetic peptide. These lines specifically lysed release cytokines (TNF-alpha, IFN-gamma, GM-CSF) response T2 MART-1(27-35), MART-1+ uncultured tumor biopsies, indicating that this epitope likely association HLA-A2 surface vivo. mediated 25- 100-fold higher lytic activity than MART-1-reactive grown presence high dose IL-2. results demonstrate peptide may represent ideal candidate Ag-specific immunotherapy