Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Applied Biochemistry and Biotechnology |
Volume | 54 |
Issue number | 2 |
Pages (from-to) | 590-601 |
Number of pages | 12 |
ISSN | 0273-2289 |
DOIs | |
Publication status | Published - Jun 2013 |
- Animals, Antibodies, Antibody Formation, Antibody Specificity, Antigens, Neoplasm, Camels, Cell Line, Tumor, Cell Surface Display Techniques, Cross Reactions, Enzyme-Linked Immunosorbent Assay, Epitopes, Glycoproteins, HT29 Cells, Humans, Male, Mice, Mucin-1, Receptor, erbB-2, Single-Domain Antibodies
Research areas
ID: 118521393