[Studies on generation of cytotoxic T lymphocytes against oral squamous carcinoma by gene-transduction of a co-stimulatory molecule, CD80].
The effect of gene-transduction of a co-stimulatory molecule, CD80, on generation of cytotoxic T lymphocytes (CTL) against oral squamous cell carcinoma (SCC) was investigated. Long-term or primarily-established short-term cultured oral SCC cell lines were transfected with the human CD80 gene using a replication-deficient recombinant adenovirus (Ad). High levels of CD80 expression were obtained in most tumor cell lines examined. Allogeneic peripheral blood mononuclear cells (PBMC) co-cultured with CD80-transduced tumor cells for 7 days elicited high cytotoxicity against melanoma (526 mel) and neuroblastoma (IMR32) cells, but not against oral SCCs (HSC3 and Ca9-22). Addition of either IL-2 or IL-12 failed to induce specific cytotoxicity against oral SCC cell lines. The combined effect of CD80-transduced tumor cells and cytokines, IL-2 and IL-12, on generation of CTL in allogeneic and autologous system was investigated. PBMC from three SCC patients elicited MHC-restricted and TCR-dependent cytotoxicity against autologous SCC, although the level of induced cytotoxicity varied. In contrast, allogeneic PBMC obtained from healthy donors exhibited non-specific cytotoxicity alone. These results suggested that CD80-transduction may be effective in oral SCC for generating tumor specific CTL in an autologous system.
Mogi
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Second Department of Oral and Maxillo-facial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University.
D000256:Adenoviridae; D018122:B7-1 Antigen / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D005822:Genetic Vectors; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D014162:Transfection
D018122:B7-1 Antigen; D007376:Interleukin-2; D018664:Interleukin-12