Recently, transgenic mice and in vitro phage display were employed to generate fully human therapeutic antibodies,. Most therapeutic antibodies developed to date were either chimeric or humanized murine antibodies due to early availability of the mouse hybridoma technology. More than two dozen therapeutic monoclonal antibodies are currently approved for the treatment of cancer and other human diseases. The MLG humanization technology described in the manuscript is an issued patent (U.S.Patent 7,462,697).ДЄntibodies are becoming a major drug modality due to the high specificity and affinity to their targets. The leading molecule (Anti-VEGF antibody) is in preclinical development for cancer therapy. The research is conducted under the strict scientific methodologies and the internal funding from Epitomics' R&D department does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Epitomics funded the research reported in this manuscript. Epitomics is a biotechnology company which is engaged in the discovery and development of therapeutic antibodies. Employees of the funder were involved in the design and execution of the experiments.Д¬ompeting interests: All authors are current or former employees of Epitomics, Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ДЇunding: This study was conducted in Epitomics, Inc. Received: OctoAccepted: JanuPublished: February 5, 2010Д¬opyright: В© 2010 Yu et al. PLoS ONE 5(2):Д®ditor: Yu Wang, Hong Kong University, Hong Kong (2010) A Humanized Anti-VEGF Rabbit Monoclonal Antibody Inhibits Angiogenesis and Blocks Tumor Growth in Xenograft Models. These studies provide proof of principle for the feasibility of developing humanized RabMAbs as therapeutics.Д¬itation: Yu Y, Lee P, Ke Y, Zhang Y, Yu Q, Lee J, et al. 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.

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. These neutralizing RabMAbs are specific to VEGF and do not cross-react to other members of the VEGF protein family. 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). Though these properties are also highly desirable for therapeutic applications, rabbit antibodies have remained untapped for human disease therapy. Rabbit antibodies have been widely used in research and diagnostics due to their high antigen specificity and affinity.

Trials fusion rabbit