抄録
Cytotoxic T lymphocytes (CTL) were induced from the peripheral blood mononuclear cells of 6 cancer patients using tumor necrosis factor-α (TNF α). Initially, TNF α (100 and 1, 000U/ml) was added at the beginning of mixed culture with tumor lymphocytes for 3 days. Then, TNF α was removed and the cells were stimulated with an immobilized anti-CD3 monoclonal antibody (1μg/ml) and interleukin-2 (1, 000U/ml) for 3-7 days.
Subsequently, the anti-CD3 antibody was removed, and the cells were incubated with 500U/ml of interleukin-2. Cells from 2 patients showed autologous tumor-killing activity before incubation with TNF α, and this activity was unchanged by TNF α. In 2 of the 4 patients without pre-existing cytotoxic T lymphocyte (CTL) activity, there was an increase of this activity after incubation with TNF α. Both CTL activity and CTL proliferation increased in accordance with the TNF α concentration.
Flow cytometric analysis revealed an increase of CD8+Leu15- cells. However, the increase in cytotoxic activity also occurred when allogeneic cancer cells were identified as target cells, suggesting that TNF α did not increase tumor specificity although it increased autologous tumor-killing acitivity. Since a high CTL activity specific to autologous tumor cells is necessary for successful CTL therapy, this subject requires further investigation.
