Cytotoxic T lymphocytes (CTL) against human lung cancer cells are difficult to induce by a conventional method using tumor cell stimulation probably due to an insufficiency of tumor antigens (TA) or costimulatory molecules such as CD80. We, therefore, investigated the potential of CD80-transfected tumor cells as stimulators of the in vitro induction of autologous tumor-specific CTL from regional lymph node lymphocytes in patients with lung cancer. Five non-small cell lung cancer cell lines (two adenocarcinomas, 1 squamous cell carcinoma, 1 large cell carcinoma and 1 adenosquamous cell carcinoma) were established from surgical specimens and were successfully transduced with a plasmid constructed with expression vector pBj and human CD80 cDNA, using a lipofection method. CD80-transfected tumor cells (CD80-AT) significantly augmented the proliferation of autologous lymphocytes from all cases as compared with non-transfected tumor cells (AT). AT-stimulated lymphocytes from 4 out of 5 cases did not show any cytotoxicity against AT;however, lymphocytes stimulated with CD80-AT exhibited substantial cytotoxicity against parental AT in all 5 cases tested. AT-stimulated lymphocytes derived from only one out of 5 cases showed major histocompatibility complex (MHC)-class I-restricted cytokine production in response to AT, while the MHC-class I-restricted responses were found in CD80-AT-stimulated lymphocytes from 4 out of 5 cases. These results indicate that CD80 on tumor cells could be a beneficial costimulatory molecule to elicit CTL against lung cancer, and also show that TA recognized by CTL was frequently expressed on lung cancer cells.

No abstract

No 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.

These results are the first demonstration of a successful induction of AT-specific T cell clones from a patient with lung adenosquamous carcinoma. It may therefore supply a possible way to apply specific immunotherapy to this type of lung cancer.