Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen. - RIIP - Réseau International des Instituts Pasteur Access content directly
Journal Articles Molecular Biotechnology Year : 2013

Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen.

Abstract

The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies that specifically recognize the TAG-72 antigen. All selected nanobodies were shown to selectively bind to this cancer-related molecule with low-nanomolar affinities and do not cross-react with other antigens, such as MUC1 or HER2. Furthermore, they can detect TAG-72 in concentrations as low as 5 U/ml which is valuable in sensitive detection of this molecule in cancerous patients. Cell ELISA experiments proved their ability for binding to the native target antigen on TAG-72 expressing cells while not showing any reactivity to HT-29 cells, a TAG-72-negative cell line. Using competition studies, we found that each nanobody recognizes a distinct epitope on the TAG-72 antigen that is different from the one recognized by the mouse anti-TAG-72 antibody, CC49. Considering their high specificity, reduced immunogenicity and multi-targeting behavior, these oligoclonal nanobodies represent a promising tool to target TAG-72 over-expressing tumor cells.
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Dates and versions

pasteur-00825965 , version 1 (25-05-2013)

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Zahra Sharifzadeh, Fatemeh Rahbarizadeh, Mohammad Ali Shokrgozar, Davoud Ahmadvand, Fereidoun Mahboudi, et al.. Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen.. Molecular Biotechnology, 2013, 54 (2), pp.590-601. ⟨10.1007/s12033-012-9601-0⟩. ⟨pasteur-00825965⟩

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