Title |
Generation and Characterization of a Diabody Targeting the αvβ6 Integrin
|
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Published in |
PLOS ONE, September 2013
|
DOI | 10.1371/journal.pone.0073260 |
Pubmed ID | |
Authors |
Heide Kogelberg, Enrique Miranda, Jerome Burnet, David Ellison, Berend Tolner, Julie Foster, Carmen Picón, Gareth J. Thomas, Tim Meyer, John F. Marshall, Stephen J. Mather, Kerry Chester |
Abstract |
The αvβ6 integrin is up-regulated in cancer and wound healing but it is not generally expressed in healthy adult tissue. There is increasing evidence that it has a role in cancer progression and will be a useful target for antibody-directed cancer therapies. We report a novel recombinant diabody antibody fragment that targets specifically αvβ6 and blocks its function. The diabody was engineered with a C-terminal hexahistidine tag (His tag), expressed in Pichia pastoris and purified by IMAC. Surface plasmon resonance (SPR) analysis of the purified diabody showed affinity in the nanomolar range. Pre-treatment of αvβ6-expressing cells with the diabody resulted in a reduction of cell migration and adhesion to LAP, demonstrating biological function-blocking activity. After radio-labeling, using the His-tag for site-specific attachment of (99m)Tc, the diabody retained affinity and targeted specifically to αvβ6-expressing tumors in mice bearing isogenic αvβ6 +/- xenografts. Furthermore, the diabody was specifically internalized into αvβ6-expressing cells, indicating warhead targeting potential. Our results indicate that the new αvβ6 diabody has a range of potential applications in imaging, function blocking or targeted delivery/internalization of therapeutic agents. |
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Mendeley readers
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Unspecified | 1 | 3% |
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