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-associated antigen CO17-1A on colorectal carcinoma cells. One of the tumor cell destruction mechanisms induced by in vivo immunotherapy with MAb17-1A has been claimed to be antibody-dependent cellular cytotoxicity (ADCC) by monocytes and NK cells. In the present study we investigated whether human neutrophils (PMN) could be involved in colorectal carcinoma cell lysis and whether IFN-gamma influences this function. We showed that neutrophils are capable of tumor lysis mediated by MAb17-1A, although to a lesser extent than are the mononuclear cells (PBMC). Neutrophil ADCC was, however, markedly increased in the presence of IFN-gamma. Enhancement by IFN-gamma was also observed for PBMC. ADCC by PMN 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 not affect MAb17-1A-mediated cytotoxicity, suggesting that receptors other than Fc gamma RIII were involved in the process. PBMC cytotoxicity was also inhibited by anti-CD16 antibodies but IFN-gamma did not overcome this effect. Finally, the scavenger enzymes superoxide dismutase and catalase did not block ADCC by PMN or PBMC, indicating that oxidants are not key factors in MAb17-1A-mediated lysis; however, in IFN-gamma-activated PMN the oxygen-dependent mechanism was in part involved in tumor lysis.
Reali
E
E
Istituto di Chimica Biologica, Università degli Studi di Ferrara, Italy.
Guiliani
A L
AL
Spisani
S
S
Moretti
S
S
Gavioli
R
R
Masucci
G
G
Gambari
R
R
Traniello
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D015179:Colorectal Neoplasms; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D051379:Mice; D009504:Neutrophils / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D017452:Receptors, IgG / Q000502:physiology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D007371:Interferon-gamma