Trageting therapy with use of anti-erb B-2 monoclonal antibodies

Abstract

The product of oncogene erb B-2 is a transmembrane type glycoprotein (Mr 185000) and has tyrosin kinase activity. It has amino acid sequence homology with EGF receptor, suggesting that p185^erbB-2 is a growth factor receptor. Monoclonal antibodies(MoAbs) were prepared to c-erb B-2 gene transfected NIH-3T3 cells (SV22) and characterized. The molecular weight of the antigen recognized with MoAbs was 180 K dalton. According to the reactivity to deletion mutants, the epitope of MoAbs was existed within No. 292 to 370 amino acids in extracellular domain of erb B-2 molecule. The distribution of erb B-2 antigen was limited and very few in normal tissues in immunohistology, while adenocarcinoma tissues expressed erb B-2 antigen. Double determinant immunoassay with two distinct anti-erb B-2 MoAbs showed that shedding erb B-2 antigen was detected in only low percentage of patient sera with malignant diseases. Furthermore, anti-erb B-2 MoAb was accumulated more in tumors than in normal organs in vivo. These results suggest that anti-erb B-2 MoAbs are of use for passive immunotherapy.