Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics
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 radioisotope...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2017
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| Online Access: | http://hdl.handle.net/1721.1/107992 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826203873445937152 |
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| author | Rashidian, Mohammad Wang, Lu Edens, Jerre G. Jacobsen, Johanne T. Hossain, Intekhab Wang, Qifan Victora, Gabriel D. Vasdev, Neil Liang, Steven H. Ploegh, Hidde |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Rashidian, Mohammad Wang, Lu Edens, Jerre G. Jacobsen, Johanne T. Hossain, Intekhab Wang, Qifan Victora, Gabriel D. Vasdev, Neil Liang, Steven H. Ploegh, Hidde |
| author_sort | Rashidian, Mohammad |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:44:39Z |
| format | Article |
| id | mit-1721.1/107992 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:44:39Z |
| publishDate | 2017 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1079922022-09-28T09:49:10Z Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics Rashidian, Mohammad Wang, Lu Edens, Jerre G. Jacobsen, Johanne T. Hossain, Intekhab Wang, Qifan Victora, Gabriel D. Vasdev, Neil Liang, Steven H. Ploegh, Hidde Massachusetts Institute of Technology. Department of Biology Ploegh, Hidde 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. Cancer Research Institute (New York, N.Y.) United States. National Institutes of Health (R01-AI087879-06) United States. National Institutes of Health (DP1-GM106409-03) United States. National Institutes of Health (R01-GM100518-04) 2017-04-10T13:10:22Z 2017-04-10T13:10:22Z 2016-01 2015-10 Article http://purl.org/eprint/type/JournalArticle 0570-0833 1521-3773 http://hdl.handle.net/1721.1/107992 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 https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1002/anie.201507596 Angewandte Chemie International Edition in English Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Rashidian, Mohammad Wang, Lu Edens, Jerre G. Jacobsen, Johanne T. Hossain, Intekhab Wang, Qifan Victora, Gabriel D. Vasdev, Neil Liang, Steven H. Ploegh, Hidde Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics |
| title | Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics |
| title_full | Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics |
| title_fullStr | Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics |
| title_full_unstemmed | Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics |
| title_short | Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics |
| title_sort | enzyme mediated modification of single domain antibodies for imaging modalities with different characteristics |
| url | http://hdl.handle.net/1721.1/107992 https://orcid.org/0000-0002-1090-6071 |
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