Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics
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Enzyme-Mediated Modification.pdf
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1.8 MB
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Author(s)
Rashidian, Mohammad
Wang, Lu
Edens, Jerre G.
Jacobsen, Johanne T.
Hossain, Intekhab
Wang, Qifan
Victora, Gabriel D.
Vasdev, Neil
Liang, Steven H.
Ploegh, Hidde
Date Issued
January 2016
Journal
Angewandte Chemie International Edition in English
Publisher
Wiley Blackwell
Citation
Rashidian, Mohammad, Lu Wang, Jerre G. Edens, Johanne T. Jacobsen, Intekhab Hossain, Qifan Wang, Gabriel D. Victora, Neil Vasdev, Hidde Ploegh, and Steven H. Liang. “Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics.” Angewandte Chemie International Edition 55, no. 2 (December 2, 2015): 528–533. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Version
Author's final manuscript
Abstract
Antibodies are currently the fastest-growing class of therapeutics. Although naked antibodies have proven valuable as pharmaceutical agents, they have some limitations, such as low tissue penetration and a long circulatory half-life. They have been conjugated to toxic payloads, PEGs, or radioisotopes to increase and optimize their therapeutic efficacy. Although nonspecific conjugation is suitable for most in vitro applications, it has become evident that site specifically modified antibodies may have advantages for in vivo applications. Herein we describe a novel approach in which the antibody fragment is tagged with two handles: one for the introduction of a fluorophore or F isotope, and the second for further modification of the fragment with a PEG moiety or a second antibody fragment to tune its circulatory half-life or its avidity. Such constructs, which recognize Class II MHC products and CD11b, showed high avidity and specificity. They were used to image cancers and could detect small tumors.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1002/anie.201507596
