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dc.contributor.authorXu, Chen
dc.contributor.authorLo, Agnes Shuk Yee
dc.contributor.authorYammanuru, Anuradha
dc.contributor.authorTallarico, Aimee St. Clair
dc.contributor.authorBrady, Kristen
dc.contributor.authorMurakami, Akikazu
dc.contributor.authorBarteneva, Natasha
dc.contributor.authorZhu, Quan Karen
dc.contributor.authorMarasco, Wayne A.
dc.date.accessioned2012-02-20T01:52:05Z
dc.date.issued2010
dc.identifier.citationXu, 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.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8191186
dc.description.abstractCarbonic 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.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0009625en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835754/pdf/en_US
dash.licenseLAA
dc.subjectimmunologyen_US
dc.subjectbiochemistryen_US
dc.subjectbiomacromolecule-ligand interactionsen_US
dc.subjectbiotechnologyen_US
dc.subjectbioengineeringen_US
dc.subjectoncologyen_US
dc.subjectoncology agentsen_US
dc.subjectrenal canceren_US
dc.subjecturologyen_US
dc.titleUnique Biological Properties of Catalytic Domain Directed Human Anti-CAIX Antibodies Discovered through Phage-Display Technologyen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorMarasco, Wayne A.
dc.date.available2012-02-20T01:52:05Z
dash.affiliation.otherHMS^Medicine- Beth Israel-Deaconessen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0009625*
dash.contributor.affiliatedLo, Agnes Shuk Yee
dash.contributor.affiliatedMarasco, Wayne
dash.contributor.affiliatedZhu, Quan


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