APOPTOSIS IN ANTIBODY-DEPENDENT MONOCYTE-MEDIATED CYTOTOXICITY WITH MONOCLONAL-ANTIBODY 17-1A AGAINST HUMAN COLORECTAL-CARCINOMA CELLS - ENHANCEMENT WITH INTERFERON-GAMMA

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been consider ed to be one of the main effector mechanisms by which unconjugated mon oclonal antibody (mAb) 17-1A can exert an antitumor effect in vivo. Si nce the apoptotic pathway as well as the necrotic pathway have been sh own to be utilized in various cytotoxic effector mechanisms, we invest igated the role of apoptosis in ADCC mediated by monocytes (ADMC) usin g mAb 17-1A as an antibody and the human colorectal carcinoma cell lin e, COLO205, as target cells in vitro. The implications of the apoptosi s during ADMC was demonstrated by means of both a DNA fragmentation as say and a TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Fu rthermore, interferon gamma (IFN gamma) was also found to enhance the induction of apoptosis significantly. The addition of superoxide dismu tase did not reduce the level of the apoptosis, although superoxide an ion (O-2-) was observed to be produced. However, the release of tumor necrosis factor alpha (TNF alpha) was significantly enhanced during AD MC, while, in addition, apoptosis was significantly inhibited by the a ddition of anti-TNF alpha antibody. These findings indicated that apop tosis might be implicated in ADMC with mAb 17-1A, which was augmented by IFN gamma, while, in addition, TNF alpha may also be one of the maj or mediators of apoptosis.