Unique Biological Properties of Catalytic Domain Directed Human Anti-CAIX Antibodies Discovered through Phage-Display Technology

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Unique Biological Properties of Catalytic Domain Directed Human Anti-CAIX Antibodies Discovered through Phage-Display Technology

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dc.contributor.author Xu, Chen
dc.contributor.author Lo, Agnes Shuk Yee
dc.contributor.author Yammanuru, Anuradha
dc.contributor.author Tallarico, Aimee St. Clair
dc.contributor.author Brady, Kristen
dc.contributor.author Murakami, Akikazu
dc.contributor.author Barteneva, Natasha
dc.contributor.author Zhu, Quan Karen
dc.contributor.author Marasco, Wayne A.
dc.date.accessioned 2012-02-20T01:52:05Z
dc.date.issued 2010
dc.identifier.citation Xu, Chen, Agnes Lo, Anuradha Yammanuru, Aimee St. Clair Tallarico, Kristen Brady, Akikazu Murakami, Natasha Barteneva, Quan Zhu, and Wayne A. Marasco. 2010. Unique Biological Properties of Catalytic Domain Directed Human Anti-CAIX Antibodies Discovered through Phage-Display Technology. PLoS ONE 5(3): e9625. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8191186
dc.description.abstract Carbonic anhydrase IX (CAIX, gene G250/MN-encoded transmembrane protein) is highly expressed in various human epithelial tumors such as renal clear cell carcinoma (RCC), but absent from the corresponding normal tissues. Besides the CA signal transduction activity, CAIX may serve as a biomarker in early stages of oncogenesis and also as a reliable marker of hypoxia, which is associated with tumor resistance to chemotherapy and radiotherapy. Although results from preclinical and clinical studies have shown CAIX as a promising target for detection and therapy for RCC, only a limited number of murine monoclonal antibodies (mAbs) and one humanized mAb are available for clinical testing and development. In this study, paramagnetic proteoliposomes of CAIX (CAIX-PMPLs) were constructed and used for anti-CAIX antibody selection from our 27 billion human single-chain antibody (scFv) phage display libraries. A panel of thirteen human scFvs that specifically recognize CAIX expressed on cell surface was identified, epitope mapped primarily to the CA domain, and affinity-binding constants (KD) determined. These human anti-CAIX mAbs are diverse in their functions including induction of surface CAIX internalization into endosomes and inhibition of the carbonic anhydrase activity, the latter being a unique feature that has not been previously reported for anti-CAIX antibodies. These human anti-CAIX antibodies are important reagents for development of new immunotherapies and diagnostic tools for RCC treatment as well as extending our knowledge on the basic structure-function relationships of the CAIX molecule. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0009625 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835754/pdf/ en_US
dash.license LAA
dc.subject immunology en_US
dc.subject biochemistry en_US
dc.subject biomacromolecule-ligand interactions en_US
dc.subject biotechnology en_US
dc.subject bioengineering en_US
dc.subject oncology en_US
dc.subject oncology agents en_US
dc.subject renal cancer en_US
dc.subject urology en_US
dc.title Unique Biological Properties of Catalytic Domain Directed Human Anti-CAIX Antibodies Discovered through Phage-Display Technology en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Marasco, Wayne A.
dc.date.available 2012-02-20T01:52:05Z
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US

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