THE INDUCTION OF CYTOTOXIC T-LYMPHOCYTES AGAINST HLA-A LOCUS-MATCHED LUNG ADENOCARCINOMA IN PATIENTS WITH NONSMALL CELL LUNG-CANCER

To induce cytotoxic T lymphocytes (CTL) against non-small cell lung ca ncer (NSCLC) efficiently, the induction of CTL was attempted using HLA -A locus-shared allogeneic NSCLC cells. T cells derived from either tu mor tissue specimens or the regional lymph nodes of patients with NSCL C were stimulated twice or three times with an HLA-A2/A24-positive NSC LC cell line (PC-9), and thereafter the cytotoxic activity was examine d by Cr-51-release assay. In patients with HLA-A24/adenocarcinoma, ant i-PC-9 cytotoxicity was induced in all 6 patients tested. Anti-PC-9 cy totoxicity was induced in 2 out of 5 patients with HLA-A2 (A24(-))/ade nocarcinoma, in 2 out of 4 patients with HLA-A24/squamous cell carcino ma, and 1 of 2 patients with HLA-A2/squamous cell carcinoma. The cytot oxic activity was observed to kill PC-9 selectively, not other NSCLC l ines, and the activity was substantially blocked by anti-MHC class I a ntibody, but not by anti-MHC class II antibody. The PC-9-specific CTL produced gamma-interferon in response to autologous tumor cells. These results indicated that the anti-PC-9 cytotoxicity was mediated by cyt otoxic T lymphocytes that may recognize the T cell epitope(s) shared a nd presented by HLA-AZ and/or HLA-A24-positive NSCLC.