A Humanized Anti-c-erbB-2 Monoclonal Antibody for the Treatment of Breast Cancer

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers that overxpress the c-erbB-2 gene. Its overexpression is also speculated to be correlated with chemoresistance to doxorubicin. The in vitro and in vivo anti-tumor effects of a humanized antibody directed against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 had direct antiproliferative activity against the SK-BR-3 cell line which overexpresses c-erbB-2. The in vivo treatment, using rhu4D5, of SCID mice carrying xenografts of 4-1ST human gastric carcinoma, which overexpresses c-erbB-2, revealed that the recombinant protein had potent anti-tumor activity. Furthermore, the cytotoxic action of human peripheral blood mononuclear cells against the SK-BR-3 cell line was significantly augmented with the administration of rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might be a more efficacious treatment than previously predicted by preclinical studies.