MACROPHAGE-COLONY-STIMULATING FACTOR ENHANCEMENT OF ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY AGAINST HUMAN COLON-CARCINOMA CELLS

Antibody-dependent cellular cytotoxicity (ADCC) has been suggested to be an important defense mechanism against tumors. The effects of recom binant human macrophage colony-stimulating factor (rhM-CSF) on ADCC ac tivity of human monocytes were investigated. Human peripheral monocyte s were pre-incubated for 72 h with rhM-CSF at various concentrations ( 50, 100, 200, 400 U/ml) and then used as effector cells in a 24-h 111- Indium release assay. Human carcinoma cell lines LS-174T, CBS, and KLE were used as targets to react with anti-carcinoma monoclonal antibodi es (mAbs: murine D612, murine CC49, and chimeric CC49). A significant increase in ADCC activity was observed after monocytes were incubated in 100-400 U/ml of human rhM-CSF. Variation in ADCC activity of monocy tes among donors was observed. The enhancement of ADCC activity was bl ocked by the addition of a neutralizing antibody to rhM-CSF. Less D612 mAb was required for the rhM-CSF-treated monocytes to mediate an equi valent level of ADCC activity as compared to the untreated monocytes. Because of the low levels of rhM-CSE required in these studies to enha nce ADCC, treatment of monocytes alone with comparable levels of rhM-C SF did not enhance antibody-independent cytotoxicity. Moreover, it is demonstrated here that recombinant human interleuken-4 (rhIL-4) and rh M-CSF can have a synergistic effect of monocyte-mediated ADCC on human tumor cells. These results thus indicate that rhM-CSF augments ADCC o f human peripheral blood monocytes using mAbs to human carcinomas, sug gesting a potential role for rhM-CSF in cancer immunotherapy.