The Induction of Cytotoxic T Lymphocytes against HLA‐A Locus‐matched Lung Adenocarcinoma in Patients with Non‐small Cell Lung Cancer

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Abstract
To induce cytotoxic T lymphocytes (CTL) against non‐small cell lung cancer (NSCLC) efficiently, the induction of CTL was attempted using HLA‐A locus‐shared allogeneic NSCLC cells. T cells derived from either tumor tissue specimens or the regional lymph nodes of patients with NSCLC were stimulated twice or three times with an HLA‐A2/A24‐positive NSCLC cell line (PC‐9), and thereafter the cytotoxic activity was examined by 51Cr‐release assay. In patients with HLA‐A24/ adenocarcinoma, anti‐PC‐9 cytotoxicity was induced in all 6 patients tested. Anti‐PC‐9 cytotoxicity was induced in 2 out of 5 patients with HLA‐A2 (A24−)/adenocarcinoma, in 2 out of 4 patients with HLA‐A24/squamous cell carcinoma, and 1 of 2 patients with HLA‐A2/squamous cell carcinoma. The cytotoxic activity was observed to kill PC‐9 selectively, not other NSCLC lines, and the activity was substantially blocked by anti‐MHC class I antibody, but not by anti‐MHC class II antibody. The PC‐9‐specific CTL produced γ‐interferon in response to autologous tumor cells. These results indicated that the anti‐PC‐9 cytotoxicity was mediated by cytotoxic T lymphocytes that may recognize the T cell epitope(s) shared and presented by HLA‐A2 and/or HLA‐A24‐positive NSCLC.