Autologous dendritic cells or cells expressing both B7-1 and MUC1 can rescue tumor-specific cytotoxic T lymphocytes from MUC1-mediated apoptotic cell death

We attempted to induce MUC1-specific cytotoxic T lymphocytes (CTLs) by mixed-lympho- cyte tumor cell culture (MLTC) using two alloge- neic MUC1-positive cancer cell lines, T-47D and MCF7. The induced CTLs exhibited MUC1-specific cytotoxicity 16 days after the initial stimulation. However, these CTLs underwent apoptotic death within 16 days. To examine whether the B7-1 mol- ecule is required for the expansion of the re- sponder cells, a B7-1(1)/MUC1(-) cell line was transfected with MUC1 cDNA, and the resulting transfectant was employed as a stimulator in an autologous MLTC. The CTLs exhibited MUC1 specificity but also continued to propagate. In par- allel, autologous dendritic cells (DCs) were added to an MLTC containing peripheral blood lympho- cytes (PBLs) and the allogeneic MUC1-positive stimulators. The CTLs demonstrated MUC1 speci- ficity and their number increased. This suggests that the B7-1 molecule is required for rescuing CTLs from MUC1-mediated apoptotic death, but not for the induction of MUC1-specific responsive- ness. This strategy to obtain the CTLs efficiently may be useful for adoptive immunotherapy against cancer. J. Leukoc. Biol. 68: 225-232; 2000.