Abstract
Despite significant progress in the clinical application of antibody drug conjugates (ADCs), novel cleavage strategies that provide improved selectivity are still needed. Herein is reported the first approach that uses near-IR light to cleave a small molecule from a biomacromolecule, and its application to the problem of ADC linkage. The preparation of cyanine antibody conjugates, drug cleavage mediated by 690 nm light, and initial in vitro and in vivo evaluation is described. These studies provide the critical chemical underpinning from which to develop this near-IR light cleavable linker strategy.
Keywords:
antibodies; conjugation; cyanines; drug delivery; fluorescence.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry*
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Antineoplastic Agents, Phytogenic / chemistry*
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Antineoplastic Agents, Phytogenic / pharmacology
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Carbocyanines / chemistry*
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Cell Line, Tumor
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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ErbB Receptors / chemistry
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Humans
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Hymecromone / analogs & derivatives
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Hymecromone / chemistry
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Hymecromone / pharmacology
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Infrared Rays
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MCF-7 Cells
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Mice
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Neoplasms, Experimental / drug therapy
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Neoplasms, Experimental / pathology
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Panitumumab
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Photolysis
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Stilbenes / chemistry*
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Stilbenes / pharmacology
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Structure-Activity Relationship
Substances
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6,8-difluoro-4-methylumbelliferyl sulfate
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Antibodies, Monoclonal
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Antineoplastic Agents, Phytogenic
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Carbocyanines
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Stilbenes
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Hymecromone
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Panitumumab
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ErbB Receptors
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fosbretabulin