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2 results on '"Fernando Jose Rebelo Do Couto"'

1. A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models.

Author

Yanlan Yu, Pierre Lee, Yaohuang Ke, Yongke Zhang, Qiu Yu, Jonathan Lee, Mingzhen Li, Jialiang Song, Jungang Chen, Jihong Dai, Fernando Jose Rebelo Do Couto, Zhiqiang An, Weimin Zhu, and Guo-Liang Yu

Subjects
Medicine, Science
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. These studies provide proof of principle for the feasibility of developing humanized RabMAbs as therapeutics.

Published
2010
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2. A humanized anti-VEGF rabbit monoclonal antibody inhibits angiogenesis and blocks tumor growth in xenograft models

Author

Guo Liang Yu, Jialiang Song, Jihong Dai, Weimin Zhu, Pierre Lee, Qiu Yu, Jonathan L.C. Lee, Yaohuang Ke, Mingzhen Li, Zhiqiang An, Fernando Jose Rebelo Do Couto, Yanlan Yu, Yongke Zhang, and Jungang Chen

Subjects
Vascular Endothelial Growth Factor A, medicine.drug_class, Angiogenesis, Molecular Sequence Data, Oncology/Oncology Agents, Antibody Affinity, Mice, Nude, lcsh:Medicine, Biology, Monoclonal antibody, Cell Line, Mice, Antibody Specificity, Cell Line, Tumor, Neoplasms, medicine, Animals, Humans, Amino Acid Sequence, Phosphorylation, lcsh:Science, Cell Proliferation, Mice, Inbred BALB C, Multidisciplinary, Neovascularization, Pathologic, Sequence Homology, Amino Acid, Cell growth, lcsh:R, Antibodies, Monoclonal, Kinase insert domain receptor, Molecular biology, Vascular Endothelial Growth Factor Receptor-2, Xenograft Model Antitumor Assays, Tumor Burden, Vascular endothelial growth factor A, Epitope mapping, Cell culture, Cancer research, biology.protein, Female, lcsh:Q, Rabbits, Antibody, Biochemistry/Drug Discovery, Epitope Mapping, Research Article, Biotechnology
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. These studies provide proof of principle for the feasibility of developing humanized RabMAbs as therapeutics.

Published
2010

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