Monoclonal anti-tumor necrosis factor (TNF) antibodies protect mouse and human cells from TNF cytotoxicity

Tumor necrosis factor (TNF) is a cytokine produced by macrophages which mediates septic shock. TNF is also associated with anti-tumor activity and is cytotoxic to many cell lines in vitro. While the clinical efficacy of anti-TNF antibodies has yet to be established, such antibodies may prevent TNF action. We have evaluated three murine monoclonal anti-TNF antibodies for their capacity to protect mouse and human cells from the cytotoxic effects of human TNF. Mouse WEHI 164 cells were tested because of their known high sensitivity to TNF. Several human cells lines were also examined: U937, HeLa, MRC5, and ME180. Two antibodies protected mouse and human cells from the cytotoxic action of TNF. The neutralizing activity was also present in the Fab fragment and insensitive to the presence of carbohydrate on the antibody. The third antibody had substantially less TNF-neutralizing activity. The relative ability of these monoclonal antibodies to protect both mouse and human cell lines from TNF-induced cell death may be an effective indicator of their in vivo efficacy.