Effective suppression of breast tumor growth by an anti-EGFR/ErbB2 bispecific antibody.
Despite the effectiveness of the anti-ErbB2 humanized antibody trastuzumab, less than 35% of patients with ErbB2-overexpressing breast cancer respond to the treatment. Here we engineered an anti-EGFR/ErbB2 bispecific antibody (TC-BsAb) using trastuzumab and cetuximab, an anti-EGFR chimeric antibody. TC-BsAb treatment led to internalization of both EGFR and ErbB2, whereas trastuzumab and cetuximab, either alone or in combination, failed to induce ErbB2 internalization. Both in vitro and in vivo experiments indicated that TC-BsAb was significantly more potent in inhibiting the growth of breast cancer cell lines than trastuzumab, cetuximab, and trastuzumab plus cetuximab, suggesting its potential use for treating breast cancer.
School of Pharmacy, The Center for Antibody Medicine of Ministry of Education, Shanghai Jiao Tong University, People's Republic of China.
Shuhui
S
Wang
Changchun
C
Chen
Yanchun
Y
Meng
Shi
S
Hu
Lei
L
Zheng
Jinjing
J
Song
Dapeng
D
Zhang
Bohua
B
Li
Yajun
Y
Guo
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000915:Antibody Affinity; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D066246:ErbB Receptors; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C512478:EGFR protein, human