Development and characterization of a fully functional small anti-HER2 antibody.
The penetrating of monoclonal antibodies (mAbs) into solid tumor may be hampered by their large size. The antibody mimetics, composed of two complementarity-determining regions (CDRs) through a cognate framework region (FR), have been demonstrated to have the capacity to penetrate tumors superior to its parental intact IgG. In this study, we used CDR and FR sequences from the humanized anti-HER2 monoclonal antibody trastuzumab to design four antibody mimetics. Then these antibody mimetics were fused to human IgG Fc to generate mimetics-Fc small antibodies. One of the four mimetics-Fc antibodies binds well to HER2-overexpressing SK-BR3 cells and effectively inhibits the binding of trastuzumab. This mimetics-Fc, denoted as HMTI-Fc, was shown to be effective in mediating antibody-dependent cellular cytotoxicity and exhibit an antiproliferative effect in SK-BR3 cells. To our knowledge, the HMTI-Fc antibody shown here is the smallest fully functional antibody and may have a potential for treatment of cancer.
Gao
Jie
J
International Joint Cancer Institute and Changhai Hospital Cancer Center, Second Military Medical University, Shanghai 200433, China.
Li
Bohua
B
Li
Huimei
H
Zhang
Xunmin
X
Zhang
Dapeng
D
Zhao
Lei
L
Wang
Chong
C
Fang
Chen
C
Qian
Weizhu
W
Hou
Sheng
S
Kou
Geng
G
Wei
Huafeng
H
Shi
Shu
S
Wang
Hao
H
Guo
Yajun
Y
D000906:Antibodies / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D000918:Antibody Specificity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D008967:Molecular Biology / Q000379:methods*; D018716:Molecular Mimicry / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology; D000068878:Trastuzumab
D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000941:Antigens; D016650:Fluorescein-5-isothiocyanate; D018719:Erb-b2 Receptor Tyrosine Kinases; D011961:Receptors, Fc; D000068878:Trastuzumab