a humanized anti-vegf rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models兔抗vegf人性化单克隆抗体抑制血管生成和块在异种移植肿瘤的生长模型.pdfVIP

A Humanized Anti-VEGF Rabbit Monoclonal Antibody Inhibits Angiogenesis and Blocks Tumor Growth in Xenograft Models 1. 2. 2. 2 2 2 3 Yanlan Yu , Pierre Lee , Yaohuang Ke , Yongke Zhang , Qiu Yu , Jonathan Lee , Mingzhen Li , 3 3 3 2 2 Jialiang Song , Jungang Chen , Jihong Dai , Fernando Jose Rebelo Do Couto , Zhiqiang An *, Weimin Zhu2, Guo-Liang Yu2 1 Department of Urology, Sir Run-Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, 2 Epitomics, Inc., Burlingame, California, United States of America, 3 Hangzhou Yikang Biotech, Inc., Hangzhou, People’s Republic of China Abstract Rabbit antibodies have been widely used in research and diagnostics due to their high antigen specificity and affinity. Though these properties are also highly desirable for therapeutic applications, rabbit antibodies have remained untapped for human disease therapy. To evaluate the therapeutic potential of rabbit monoclonal antibodies (RabMAbs), we generated a panel of neutralizing RabMAbs against human vascular endothelial growth factor-A (VEGF). These neutralizing RabMAbs are specific to VEGF and do not cross-react to other members of the VEGF protein family. Guided by sequence and lineage analysis of a panel of neutralizing RabMAbs, we humanized the lead candidate by substituting non-critical residues with human residues within both the frameworks and the CDR regions. We showed that the humanized RabMAb retained its parental biological properties and showed potent inhibition of the growth of H460 lung carcinoma and A673 rhabdomyosarcoma xenografts in mice. Th