INTERFERON-GAMMA ENHANCES MONOCLONAL-ANTIBODY 17-1A-DEPENDENT NEUTROPHIL CYTOTOXICITY TOWARD COLORECTAL-CARCINOMA CELL-LINE SW11-16

17-1A is a murine monoclonal antibody (MAb) specific for the tumor-ass ociated antigen CO17-1A on colorectal carcinoma cells. One of the tumo r cell destruction mechanisms induced by in vivo immunotherapy with MA b17-1A has been claimed to be antibody-dependent cellular cytotoxicity (ADCC) by monocytes and NK cells. In the present study we investigate d whether human neutrophils (PMN) could be involved in colorectal carc inoma cell lysis and whether IFN-gamma influences this function. We sh owed that neutrophils are capable of tumor lysis mediated by MAb17-1A, although to a lesser extent than are the mononuclear cells (PBMC). Ne utrophil ADCC was, however, markedly increased in the presence of IFN- gamma. Enhancement by IFN-gamma was also observed for PBMC. ADCC by PM N required the binding of MAb17-1A to Fc gamma RIII (CD16) since anti- Fc gamma RIII MAbs efficiently blocked tumor cell lysis. In contrast, in the presence of IFN-gamma the neutralization of Fc gamma RIII did n ot affect MAb17-1A-mediated cytotoxicity, suggesting that receptors ot her than Fc gamma RIII were involved in the process. PBMC cytotoxicity was also inhibited by anti-CD16 antibodies but IFN-gamma did not over come this effect. Finally, the scavenger enzymes superoxide dismutase and catalase did not block ADCC by PMN or PBMC, indicating that oxidan ts are not key factors in MAb17-1A-mediated lysis; however, in IFN-gam ma-activated PMN the oxygen-dependent mechanism was in part involved i n tumor lysis. (C) 1994 Academic Press, Inc.