Autologous dendritic cells or cells expressing both B7-1 and MUC1 can rescue tumor-specific cytotoxic T lymphocytes from MUC1-mediated apoptotic celldeath
K. Kontani et al., Autologous dendritic cells or cells expressing both B7-1 and MUC1 can rescue tumor-specific cytotoxic T lymphocytes from MUC1-mediated apoptotic celldeath, J LEUK BIOL, 68(2), 2000, pp. 225-232
We attempted to induce MUC1-specific cytotoxic T lymphocytes (CTLs) by mixe
d-lymphocyte tumor cell culture (MLTC) using two allogeneic MUC1-positive c
ancer cell lines, T-47D and MCF7. The induced CTLs exhibited MUC1-specific
cytotoxicity 16 days after the initial stimulation. However, these CTLs und
erwent apoptotic death within 16 days. To examine whether the B7-1 molecule
is required for the expansion of the responder cells, a B7-1(+)/MUC1(-) ce
ll line was transfected with MUC1 cDNA, and the resulting transfectant was
employed as a stimulator in an autologous MLTC. The CTLs exhibited MUC1 spe
cificity but also continued to propagate. In parallel, autologous dendritic
cells (DCs) were added to all MLTC containing peripheral blood lymphocytes
(PBLs) and the allogeneic MUC1-positive stimulators. The CTLs demonstrated
MUC1 specificity and their number increased. This suggests that the B7-1 m
olecule is required for rescuing CTLs front MUC1-mediated apoptotic death,
but not for the induction of MUC1-specific responsiveness. This strategy to
obtain the CTLs efficiently may be useful for adoptive immunotherapy again
st cancer.