M-CSF GENE TRANSDUCTION IN MULTIDRUG-RESISTANT HUMAN CANCER-CELLS TO ENHANCE ANTI-P-GLYCOPROTEIN ANTIBODY-DEPENDENT MACROPHAGE-MEDIATED CYTOTOXICITY

A human macrophage-colony-stimulating-factor(M-CSF) gene inserted into an expression vector (pRc/CMV-MCSF) was transfected into multidrug-re sistant (MDR) human ovarian cancer cells (AD10) to induce secretion of human M-CSF into the medium. The M-CSF level in the culture medium of the transfected cells reached 100 ng/ml after 7 days, and the ability of the cells to secrete M-CSF was stable for at least 3 months. Trans fection of the M-CSF gene did not result in any change in expression o f MDRI (P-glycoprotein), proliferation or chemosensitivity of the cell s from those of the parent cells. There was also no difference between the transfected and the parent cells in susceptibility to NK cell- or interleukin-2-activated killer-cell-mediated cytotoxicity. Human bloo d monocytes that had been incubated for 4 days in medium with the cult ure supernatant of MH-AD10 cells exhibited higher ADCC activity than u ntreated monocytes against MDRI -positive cancer cells. This effect of the supernatant of AD10 cells was completely abolished by its treatme nt with a monoclonal anti-M-CSF antibody (MAb). When transfected human MDR cells were injected into nude mice, an inverse correlation was se en between the ability of the cells to produce M-CSF and their tumorig enicity. Thus, gene modification of MDR cancer cells seems hopeful as a therapeutic method for enhancing anti-MDRI-MAb-dependent macrophage- mediated cytotoxicity against human MDR cancer cells. (C) 1993 Wiley-L iss, Inc.