IDENTIFICATION AND CHARACTERIZATION OF A TNF-ALPHA ANTAGONIST DERIVEDFROM A MONOCLONAL-ANTIBODY

Peptides derived from the CDRs of the anti-TNF alpha monoclonal antibo dy Di62 were tested for inhibition of binding of Di62 to TNF alpha as well as of TNF alpha to its 55 and 75 kDa receptor. A peptide derived from the CDR1 of the light chain was shown to specifically inhibit Di6 2 binding to TNF alpha with markedly higher activity (K-i = 4 mu M) th an all other CDR-derived peptides. This peptide also significantly inh ibited binding of TNF alpha to its 55 and 75 kDa receptor and protecte d L929 cells from the cytotoxic effect of TNF alpha (IC50 = 6 mu M). T he C-terminal region of this peptide, which is homologous to the 55 an d 75 kDa TNF receptor, was found to be essential for activity.