AUTOCRINE INHIBITION OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR BY INTRACELLULAR EXPRESSION OF A SINGLE-CHAIN ANTIBODY

A gene encoding a single-chain antibody which specifically binds the h uman epidermal growth factor (EGF) receptor has been constructed and e xpressed intracellularly. The single-chain antibody is derived from mo noclonal antibody 225 which competes with EGF for binding to the extra cellular domain of the receptor. The single-chain antibody was provide d with a signal peptide to direct it to the secretory pathway and was expressed in EGF receptor transformed NIH/3T3 fibroblasts. EGF induced activation of its receptor was reduced in these cells. In addition, E GF-induced anchorage-independent growth of the cells was inhibited. Th e data suggest that the single-chain antibody functions in an autocrin e fashion to inhibit the activity of the EGF receptor. (C) 1994 Academ ic Press, Inc.