A Humanized Anti-VEGF Rabbit Monoclonal Antibody Inhibits Angiogenesis and Blocks Tumor Growth in Xenograft Models
作者： Yanlan Yu , Pierre Lee , Yaohuang Ke , Yongke Zhang , Qiu Yu
DOI: 10.1371/JOURNAL.PONE.0009072
关键词:
摘要: Rabbit antibodies have been widely used in research and diagnostics due to their high antigen specificity affinity. Though these properties are also highly desirable for therapeutic applications, rabbit remained untapped human disease therapy. To evaluate the potential of monoclonal (RabMAbs), we generated a panel neutralizing RabMAbs against vascular endothelial growth factor-A (VEGF). These specific VEGF do not cross-react other members protein family. Guided by sequence lineage analysis RabMAbs, humanized lead candidate substituting non-critical residues with within both frameworks CDR regions. We showed that RabMAb retained its parental biological potent inhibition H460 lung carcinoma A673 rhabdomyosarcoma xenografts mice. studies provide proof principle feasibility developing as therapeutics.
harvard.edu
researchgate.net 
sci-hub.se 参考文章(56)
Noel Weidner, Judah Folkman, Franco Pozza, Pierantonio Bevilacqua, Elizabeth N. Allred, Dan H. Moore, Salvatore Meli, Giampietro Gasparini, Tumor Angiogenesis: A New Significant and Independent Prognostic Indicator in Early-Stage Breast Carcinoma Journal of the National Cancer Institute. ,vol. 84, pp. 1875- 1887 ,(1992) , 10.1093/JNCI/84.24.1875
Guo-Zhong Tao, Ikuo Nakamichi, Nam-On Ku, Jing Wang, Maria Frolkis, Xiaosong Gong, Weimin Zhu, Robert Pytela, M. Bishr Omary, Bispecific and human disease-related anti-keratin rabbit monoclonal antibodies. Experimental Cell Research. ,vol. 312, pp. 411- 422 ,(2006) , 10.1016/J.YEXCR.2005.11.010
T. Sitnikova, C. Su, Coevolution of immunoglobulin heavy- and light-chain variable-region gene families. Molecular Biology and Evolution. ,vol. 15, pp. 617- 625 ,(1998) , 10.1093/OXFORDJOURNALS.MOLBEV.A025965
Xiaolei Zhu, Shenhong Wu, William L. Dahut, Chirag R. Parikh, Risks of Proteinuria and Hypertension With Bevacizumab, an Antibody Against Vascular Endothelial Growth Factor: Systematic Review and Meta-Analysis American Journal of Kidney Diseases. ,vol. 49, pp. 186- 193 ,(2007) , 10.1053/J.AJKD.2006.11.039
Paul J. Carter, Potent antibody therapeutics by design Nature Reviews Immunology. ,vol. 6, pp. 343- 357 ,(2006) , 10.1038/NRI1837
M. A. Roguska, J. T. Pedersen, C. A. Keddy, A. H. Henry, S. J. Searle, J. M. Lambert, V. S. Goldmacher, W. A. Blattler, A. R. Rees, B. C. Guild, Humanization of murine monoclonal antibodies through variable domain resurfacing Proceedings of the National Academy of Sciences of the United States of America. ,vol. 91, pp. 969- 973 ,(1994) , 10.1073/PNAS.91.3.969
Nils Lonberg, Human antibodies from transgenic animals. Nature Biotechnology. ,vol. 23, pp. 1117- 1125 ,(2005) , 10.1038/NBT1135
Peter T. Jones, Paul H. Dear, Jefferson Foote, Michael S. Neuberger, Greg Winter, Replacing the complementarity-determining regions in a human antibody with those from a mouse Nature. ,vol. 321, pp. 522- 525 ,(1986) , 10.1038/321522A0
Napoleone Ferrara, None, Vascular endothelial growth factor: basic science and clinical progress. Endocrine Reviews. ,vol. 25, pp. 581- 611 ,(2004) , 10.1210/ER.2003-0027
H. Spieker-Polet, P. Sethupathi, P. C. Yam, K. L. Knight, Rabbit monoclonal antibodies: generating a fusion partner to produce rabbit-rabbit hybridomas Proceedings of the National Academy of Sciences of the United States of America. ,vol. 92, pp. 9348- 9352 ,(1995) , 10.1073/PNAS.92.20.9348