A humanized Anti-c-erbB-2 monoclonal antibody for the treatment of breast cancer |
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| Authors: | Yutaka Tokuda Akira Okumura Masatoshi Ohta Mitsuhiro Kubota Yasuyuki Ohnishi Kazuo Shmamura Masumi Yoshimura Yoshito Ueyama Norikazu Tamaoki Tomoo Tajima |
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| Affiliation: | (1) Department of Surgery, Tokai University School of Medicine, 259-11, Isehara, Japan;(2) Department of Pathology, Tokai University School of Medicine, 259-11, Isehara, Japan;(3) Central Institute for Experimental Animals, 259-11, Isehara, Japan;(4) Kanagawa Academy of Science and Technology, 259-11 Bohseidai, Isehara, Japan |
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| Abstract: | The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers that overexpress 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. |
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| Keywords: | c-erbB-2 Humanized monoclonal antibody Anti-tumor effect SCID mice |
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