Isolation and characterization of human anti-VEGF165 monoclonal antibody with anti-tumor efficacy from transgenic mice expressing human immunoglobulin loci.
The purpose of this study was to prepare a fully human anti-VEGF (vascular endothelial growth factor) monoclonal antibody with anti-tumor activity from five-feature mice which express human immunoglobin loci. Four hybridomas secreting mAb stably were isolated successfully. Some characters such as isotypes, cross-reactivity, inhibition on the binding of hVEGF to VEGFR-2, dissociation constants and the idiotypic characteristic were determined. Proliferation of T24 and Ls-174-T cell line and nude mice bearing human colorectal cancer were used to evaluate therapeutic effects and safety of this mAb. Pharmacokinetics data shows the half life of this mAb was about 5 days after a single intravenous injection. These results suggest the fully human anti-VEGF mAb maybe safe and efficient for cancer treatment.
Liu
Yu
Y
Department of biochemistry, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing 210009, PR China. liuyu713@gmail.com
Yun
Dong-jie
DJ
Chen
Jian-quan
JQ
Zhao
Jian-yang
JY
Liu
Si-guo
SG
Cheng
Guo-xiang
GX
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007075:Immunoglobulin M; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A