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Biochem Biophys Res Commun. 2013 Jul 5;436(3):543-50. doi: 10.1016/j.bbrc.2013.06.007. Epub 2013 Jun 11.

Development of humanized rabbit monoclonal antibodies against vascular endothelial growth factor receptor 2 with potential antitumor effects.

Author information

1
Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. yanlanyu@gmail.com

Abstract

Vascular endothelial growth factor-A (VEGF-A) plays a critical role in physiologic and pathologic angiogenesis through its receptors especially through VEGFR2. The lack of cross-reactivity of monoclonal antibodies with human VEGFR2/mouse Flk-1 is a major obstacle in preclinical developments. In this study, using a unique hybridoma technique, we generated a panel of 30 neutralization anti-VEGFR2 rabbit monoclonal antibodies (RabMAbs) either blocking VEGF/VEGFR2 interaction or inhibiting VEGF-stimulated VEGFR2 tyrosine kinase phosphorylation. Among 18 RabMAbs with human/mouse VEGFR2 cross-reactivity, we humanized one lead candidate RabMAb by Mutational Lineage Guided (MLG) method and further demonstrated its potent inhibition of tumor growth in xenograft mouse model. Our study suggests that RabMAbs are highly relevant for therapeutic applications.

KEYWORDS:

Angiogenesis; Anti-angiogenic therapy; Rabbit monoclonal antibody; Vascular endothelial growth factor receptor 2

PMID:
23770369
DOI:
10.1016/j.bbrc.2013.06.007
[Indexed for MEDLINE]
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