GM-CSF augments the IL-4-induced cytotoxic activity of human mononuclear cells in the presence of the mouse monoclonal antibody 17-1A

Background - The therapeutic effect of various modulators of the immune system might be increased if they are combined. Information on their activity using different schedules may be obtained from in vitro analyses. Methods - In this study, human peripheral blood mononuclear cells (lymphocytes and monocytes)(PBMC) were treated at the same time or sequentially with GM-CSF and IL-4 for different periods. Cytokine-activated PBMC were tested for cytolytic activity in a 18-h antibody-dependent cellular cytotoxicity (ADCC) assay using MAb 17-1A (mouse IgG2a) against SW1116 (a human colorectal carcinoma cell line). Results - The simultaneous incubation of effector cells with both cytokines did not increase the cytotoxicity induced by IL-4 or GM- CSF separately. Priming of PBMC with GM-CSF at the optimal concentration (10-3 μg/ml) for 1, 2 and 4h significantly enhanced the subsequent IL-4 induced activation of PBMC used at the optimal concentration (10-3 μg/ml). GM-CSF also augmented the cytotoxicity at a suboptimal concentration (10-4 μg/ml), but the lytic capability was less pronounced. Initial exposure of PBMC to IL-4 at optimal or suboptimal concentrations followed by stimulation with GM-CSF had no synergistic effect on ADCC. Conclusions - These results might have relevance as preliminary information to exploit the concept of combining different biological therapeutic agents for clinical protocols in cancer patients.