IL-2 GENE-TRANSDUCED HUMAN HLA-A2 MELANOMA-CELLS CAN GENERATE A SPECIFIC ANTITUMOR CYTOTOXIC T-LYMPHOCYTE RESPONSE

This study was designed to assess whether transfer of the interleukin- 2 (IL-2) gene into human tumor cells could generate cytotoxic T lympho cytes (CTL) directed specifically against the autologous tumor. Two HL A class I+ melanoma cell lines, one (TOM) A2+ and the other (CLB-M) A2 -, obtained from living patients were transduced with the IL-2 gene. T he patients' peripheral blood lymphocytes (PBL) were incubated with ir radiated IL-2 gene-transduced autologous tumor cells for up to four we eks. After seven days, PBL from both patients showed non-specific cyto toxic activity against the K562 cell line. When the co-culture incubat ion time was prolonged to 28 days, PBL from patient TOM (A2+) develope d a lytic activity directed specifically against the autologous tumor cells. In contrast, after 28 days of incubation, PBL from CLB-M (A2-) displayed only non-specific cytotoxic activity. Inhibition experiments demonstrated that the specific lytic function observed with TOM cells transduced with the IL-2 gene could be reversed following incubation with monoclonal antibodies directed against HLA class I and CD8. The e vidence that K562 cells were incapable of blocking the PBL killing cap acity in a cold-target inhibition assay further confirmed that enginee red TOM cells induced the generation of specific CTL. This study indic ates that retroviral vector mediated transfer of the IL-2 gene into hu man melanoma cell lines can lead to the amplification of the autologou s cytotoxic compartment and to the generation of specific antitumor CT L, and that the A2 allele may play an important role in the process of tumor recognition.