Autologous Tumor‐specific Cytotoxic T Lymphocytes in a Patient with Lung Adenocarcinoma: Implications of the Shared Antigens Expressed in HLA‐A24 Lung Cancer Cells

Human lung adenocarcinoma‐specific cytotoxic T lymphocytes (CTL) were generated by multiple stimulations with autologous tumor cells (named A110L) from regional lymph node lymphocytes and tumor‐infiltrating lymphocytes expanded by solid‐phase anti‐CD3 monoclonal antibody (mAb) and recombinant interleukin‐2. The CTL lysed A110L but failed to kill either autologous B lymphocytes immortalized by the Epstein‐Barr virus or K562. The killing activity of the CTL against autologous A110L was inhibited by anti‐MHC class I mAb (W6/32), but not by anti‐MHC class II mAb. The CTL produced interferon‐γ and GM‐CSF in response to A110L and the production was completely blocked by the addition of anti‐MHC class I mAb. The HLA type of the CTL was HLA‐A2/A24, B52/B54, Cw1/‐. Allele‐specific deletion of HLA‐A2 molecules was observed in A110L by staining with anti‐HLA‐A2 mAb. A partial blocking effect on the cytokine production from the CTL was also obtained with anti‐CD8, and anti‐HLA‐A24 mAbs, but not with anti‐MHC class II, anti‐CD4 and anti‐HLA‐A2 mAbs. To analyze further the mechanism of antigen recognition by the CTL, the cross reactivity of the CTL against several HLA‐A locus‐matched (HLA‐A24+) and mismatched allogeneic tumor cells (HLA‐A24‐) was investigated. The A110L‐specific CTL showed a weak but significant cytotoxicity against some HLA‐A24 positive lung cancer cell lines, such as Sq‐1 (HLA‐A11/A24, squamous cell carcinoma) and PC‐9 (HLA‐A2/A24, adenocarcinoma), but failed to kill HLA‐A locus‐mismatched allogeneic tumors. This cross reactivity of the CTL against Sq‐1 and PC‐9 was blocked by anti‐MHC class I mAb. These results thus demonstrate that shared common tumor antigens might exist among lung cancer cells in the context of HLA‐A24.