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  FRET Reagent Reveals the Intracellular Processing of Peptide-Linked Antibody-Drug Conjugates

Lee, B.-C., Chalouni, C., Doll, S., Nalle, S. C., Darwish, M., Tsai, S. P., et al. (2018). FRET Reagent Reveals the Intracellular Processing of Peptide-Linked Antibody-Drug Conjugates. Bioconjugate Chemistry, 29(7), 2468-2477. doi:10.1021/acs.bioconjchem.8b00362.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-03F6-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-03F7-4
Genre: Journal Article

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 Creators:
Lee, Byoung-Chul1, Author
Chalouni, Cecile1, Author
Doll, Sophia2, Author              
Nalle, Sam C.1, Author
Darwish, Martine1, Author
Tsai, Siao Ping1, Author
Kozak, Katherine R.1, Author
Del-Rosario, Geoffrey1, Author
Yu, Shang-Fan1, Author
Erickson, Hans1, Author
Vandlen, Richard1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: METASTATIC BREAST-CANCER; NON-HODGKIN-LYMPHOMA; TRASTUZUMAB EMTANSINE; THERAPEUTIC ACTIVITY; BRENTUXIMAB VEDOTIN; PROSTATE-CANCER; CYTOTOXIC DRUG; SOLID TUMORS; PHASE-II; AURISTATINBiochemistry & Molecular Biology; Chemistry;
 Abstract: Despite the recent success of antibody-drug conjugates (ADCs) in cancer therapy, a detailed understanding of their entry, trafficking, and metabolism in cancer cells is limited. To gain further insight into the activation mechanism of ADCs, we incorporated fluorescence resonance energy transfer (FRET) reporter groups into the linker connecting the antibody to the drug and studied various aspects of intracellular ADC processing mechanisms. When comparing the trafficking of the antibody FRET drug conjugates in various different model cells, we found that the cellular background plays an important role in how the antigen mediated antibody is processed. Certain tumor cells showed limited cytosolic transport of the payload despite efficient linker cleavage. Our FRET assay provides a facile and robust assessment of intracellular ADC activation that may have significant implications for the future development of ADCs.

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Language(s): eng - English
 Dates: 2018-062018
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Degree: -

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Title: Bioconjugate Chemistry
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 29 (7) Sequence Number: - Start / End Page: 2468 - 2477 Identifier: ISSN: 1043-1802
CoNE: /journals/resource/954925589391