PMID: 9533541May 14, 1998Paper

Efficient generation of autologous peripheral blood-derived cytotoxic T lymphocytes against poorly immunogenic human tumors using recombinant CD80-adenovirus together with interleukin 12 and interleukin 2

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
S MogiM Azuma

Abstract

To generate CTLs against poorly immunogenic human tumor cells, we transfected the human CD80 gene into the tumor cells using a replication-deficient adenovirus (Ad) vector. The successful surface expression of CD80 was obtained in both cultured tumor cell lines and primary cultured tumor cells. Transduction of CD80 alone was not sufficient to induce cytotoxicity of peripheral blood lymphocytes against allogeneic tumor cell lines except for melanoma cells. We, therefore, investigated a combined effect of CD80-Ad-infected tumor cells and interleukin 12 (IL-12). Although 7-day cultivation of autologous or allogeneic lymphocytes with CD80-Ad-infected tumor cells and IL-12 slightly enhanced cytotoxicity against some allogeneic tumor cells, no substantial cytotoxicity was observed against autologous tumor cells. When we extended the culture period to 14 days in the presence of IL-2, a prominent enhancement of cytotoxicity was observed against both allogeneic and autologous tumor cells. Cytotoxicity against autologous tumor cells, but not against allogeneic tumor cells, was efficiently inhibited by anti-CD3 monoclonal antibody. Furthermore, the selective cytotoxicity against a panel of targets indicated that the induced CTLs recognize...Continue Reading

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