title: Near-IR Light-Mediated Cleavage of Antibody-Drug Conjugates Using Cyanine Photocages.
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.
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD (USA).
authors.forename: Roger R
authors.initials: RR
authors.lastname: Nani
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD (USA).
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Gorka
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD (USA).
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD (USA).
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD (USA). martin.schnermann@nih.gov.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schnermann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D002232:Carbocyanines / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000737:chemistry; D006801:Humans; D006923:Hymecromone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D007259:Infrared Rays; D061986:MCF-7 Cells; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D000077544:Panitumumab; D010782:Photolysis; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C504401:6,8-difluoro-4-methylumbelliferyl sulfate; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D002232:Carbocyanines; D013267:Stilbenes; D006923:Hymecromone; D000077544:Panitumumab; D066246:ErbB Receptors; C058728:fosbretabulin
keywords: antibodies; conjugation; cyanines; drug delivery; fluorescence