Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology

Chen Xu, Agnes Lo, Anuradha Yammanuru, Aimee St Clair Tallarico, Kristen Brady, Akikazu Murakami, Natasha Barteneva, Quan Zhu, Wayne A. Marasco

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Carbonic anhydrase IX (CAIX, gene G250/MN-encoded transmembrane protein) is highly expressed in various human epithelial tumors such as renal clear cell carc inoma (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.

Original languageEnglish
Article numbere9625
JournalPLoS One
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 10 2010
Externally publishedYes

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Bacteriophages
active sites
bacteriophages
Anti-Idiotypic Antibodies
Catalytic Domain
Carbonic Anhydrases
Display devices
Technology
antibodies
Antibodies
Tumors
Monoclonal Antibodies
carbonate dehydratase
Single-Chain Antibodies
Signal transduction
Chemotherapy
Radiotherapy
Biomarkers
monoclonal antibodies
Epitopes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Xu, C., Lo, A., Yammanuru, A., Tallarico, A. S. C., Brady, K., Murakami, A., ... Marasco, W. A. (2010). Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology. PLoS One, 5(3), [e9625]. https://doi.org/10.1371/journal.pone.0009625

Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology. / Xu, Chen; Lo, Agnes; Yammanuru, Anuradha; Tallarico, Aimee St Clair; Brady, Kristen; Murakami, Akikazu; Barteneva, Natasha; Zhu, Quan; Marasco, Wayne A.

In: PLoS One, Vol. 5, No. 3, e9625, 10.03.2010.

Research output: Contribution to journalArticle

Xu, Chen ; Lo, Agnes ; Yammanuru, Anuradha ; Tallarico, Aimee St Clair ; Brady, Kristen ; Murakami, Akikazu ; Barteneva, Natasha ; Zhu, Quan ; Marasco, Wayne A. / Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology. In: PLoS One. 2010 ; Vol. 5, No. 3.
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