Enhancement of lymphokine-activated killer cell induction using anti-CD25 and anti-CTLA-4 monoclonal antibodies

Immunosuppression may contribute to cancer progression, in which regulatory T (T-reg) cells have been demonstrated to play important roles. We investigated whether anti-CD25 (a-CD25) monoclonal antibody (mAb) and anti-cytotoxic T lymphocyte-associated antigen-4 (a-CTLA-4) mAb could augment in vitro proliferation and cytotoxic activity against cancer cell lines of lymphokine-activated killer (LAK) cells. Human LAK cells with immobilized α-CD3 Ab plus IL-2 were significantly augmented, including LAK/a-CD25 (10 μg ml, p=0.045) and LAK/a-CTLA-4 (5 μg/ml, p=0.025; 10 μg/ml, p=0.019). LAK/a-CD25 and LAK/a-CTLA-4 showed significant cytotoxic activities against gastric cancer cell lines (p<0.05). The phenotype of LAK cells showed that α-CD25 and α-CTLA-4 mAb more selectively induced the phenotype of CD8 + cells. The secretion of IFN-y increased significantly in LAK/a-CTLA-4 (p=0.032). α-CD25 mAb reduced intracellular CTLA-4 (p=0.0069), and α-CTLA-4 mAb reduced intracellular FOXP3 (p=0.049), respectively. These results suggest that LAK cells are highly augmented in the presence of α-CD25 mAb and α-CTLA-4 mAb through the possible mechanism of the suppression of T-reg.