Effect of B7.1-transfected human colon cancer cells on the induction of autologous tumour-specific cytotoxic T cells

Background: The induction of tumour-specific immunity is important for adva nced cancer therapy. There are many molecules, including costimulatory mole cules, that have been identified as the activator for tumour-specific T cel ls. Methods: To induce autologous tumour-specific cytotoxic T lymphocytes (CTL) more effectively, we studied whether the expression of the B7 gene may ren der human colon cancer cells able to stimulate autologous peripheral blood mononuclear cells (PBMC) to become tumour-specific cytotoxic T cells. After the establishment of a B7.1 gene transfected tumour cell line, Cw2/B7.1, w e first examined its stimulatory effect on autologous PBMC and subsequently , its effect on the induction of parental cell (Cw2)-specific CTL. Results: The results showed that Cw2/B7.1. had a more potent stimulatory ef fect on PBMC for the induction of both proliferation and cytotoxicity than Cw2. By adding a low dose of interleukin-2, Cw2/B7.1-activated killer cell activity was significantly increased. The specificity of Cw2/B7.1-activated killer cells was demonstrated by the absence of their cytotoxicity to eith er human lymphocyte antigen (HLA)-A33 identical (ORF) or HLA-non-identical (MT) allogenic colon cancer cell lines. Furthermore, such Cw2-specific cyto toxic activity was significantly reduced by the deletion of CD8(+) cells bu t not CD4(+) cells, indicating that these killer cells were mainly CD8(+) T cells. Conclusions: Thus, our results demonstrate that, by using B7.1 gene-transfe cted tumour cell lines, we effectively induced autologous tumour-specific C TL. These results will provide us with new tools for adoptive immunotherapy for colon cancer patients. (C) 1999 Blackwell Science Asia Pry Ltd.