TRANSFECTION OF IL-2 AUGMENTS CTL RESPONSE TO HUMAN-MELANOMA CELLS IN-VITRO - IMMUNOLOGICAL CHARACTERIZATION OF A MELANOMA VACCINE

We have transfected human melanoma cell line 518A2 with the cDNA encod ing interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF), and compared cytokine-producing clones for their abil ity to induce melanoma-specific cytotoxic T lymphocytes (CTL) from aut ologous peripheral blood mononuclear cells (PBMC) in vitro. The parent al cell line expressed HLA-AI, HLA-A2, ICAM-1, LFA-S, in addition to t he common CT, antigens MAGE-1, MAGE-3, tyrosinase, gp100, and Melan-A/ MART-1. Stimulation of autologous PBMC responders with the IL-2-transf ected clone 518/IL2.14 specifically induced CTL lines reactive with al l cell lines derived from the autologous patient. Strikingly, GM-CSF-t ransfected 518A2 cells did not induce anti-tumor CTL reactivity. CTL i nduction against 518/IL2.14 was independent of HLA class II expression or CD4 help. The parental cell line 518A2 gained immunogenic properti es when high concentrations of IL-2 were supplied exogenously, indicat ing that IL-2 produced and present at high levels locally by itself en hanced immunogenicity. From the autologous CTL line reactive with 518/ IL2.14, clones were generated against an as yet unknown antigen, which was present in all autologous melanoma cell lines as well as in 7 of 15 HLA-A2(+) melanoma cell lines tested, but not in melanocytes. These results will be discussed with respect to the possibility of using IL -2-transfected melanoma cells as a vaccine for treatment of patients w ith melanoma.