Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10758802 | Biochemical and Biophysical Research Communications | 2013 | 25 Pages |
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.
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Authors
Yanlan Yu, Pierre Lee, Yaohuang Ke, Yongke Zhang, Jungang Chen, Jihong Dai, Mingzhen Li, Weimin Zhu, Guo-Liang Yu,