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Interlaboratory Study for Characterizing Monoclonal Antibodies by Top-Down and Middle-Down Mass Spectrometry.
Journal article

Interlaboratory Study for Characterizing Monoclonal Antibodies by Top-Down and Middle-Down Mass Spectrometry.

  • Srzentić K Northwestern University, Evanston, Illinois 60208-0001, United States.
  • Fornelli L Northwestern University, Evanston, Illinois 60208-0001, United States.
  • Tsybin YO Spectroswiss, EPFL Innovation Park, Building I, 1015 Lausanne, Switzerland.
  • Loo JA University of California-Los Angeles, Los Angeles, California 90095, United States.
  • Seckler H Northwestern University, Evanston, Illinois 60208-0001, United States.
  • Agar JN Northeastern University, Boston, Massachusetts 02115, United States.
  • Anderson LC National High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.
  • Bai DL University of Virginia, Charlottesville, Virginia 22901, United States.
  • Beck A Centre d'immunologie Pierre Fabre, 74160 Saint-Julien-en-Genevois, France.
  • Brodbelt JS University of Texas at Austin, Austin, Texas 78712-1224, United States.
  • van der Burgt YEM Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
  • Chamot-Rooke J Institute Pasteur, 75015 Paris, France.
  • Chatterjee S University of Antwerp, 2000 Antwerp, Belgium.
  • Chen Y Biogen, Inc., Cambridge, Massachusetts 02142-1031, United States.
  • Clarke DJ The University of Edinburgh, EH9 3FJ Edinburgh, United Kingdom.
  • Danis PO Consortium for Top-Down Proteomics, Cambridge, Massachusetts 02142, United States.
  • Diedrich JK The Scripps Research Institute, La Jolla, California 92037, United States.
  • D'Ippolito RA University of Virginia, Charlottesville, Virginia 22901, United States.
  • Dupré M Institute Pasteur, 75015 Paris, France.
  • Gasilova N Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Ge Y University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
  • Goo YA University of Maryland, Baltimore, Maryland 21201, United States.
  • Goodlett DR University of Maryland, Baltimore, Maryland 21201, United States.
  • Greer S University of Texas at Austin, Austin, Texas 78712-1224, United States.
  • Haselmann KF Novo Nordisk, DK-2760 Malov, Denmark.
  • He L National High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.
  • Hendrickson CL National High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.
  • Hinkle JD University of Virginia, Charlottesville, Virginia 22901, United States.
  • Holt MV Baylor College of Medicine, Houston, Texas 77030-3411, United States.
  • Hughes S The University of Edinburgh, EH9 3FJ Edinburgh, United Kingdom.
  • Hunt DF University of Virginia, Charlottesville, Virginia 22901, United States.
  • Kelleher NL Northwestern University, Evanston, Illinois 60208-0001, United States.
  • Kozhinov AN Spectroswiss, EPFL Innovation Park, Building I, 1015 Lausanne, Switzerland.
  • Lin Z University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
  • Malosse C Institute Pasteur, 75015 Paris, France.
  • Marshall AG National High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.
  • Menin L Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
  • Millikin RJ University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
  • Nagornov KO Spectroswiss, EPFL Innovation Park, Building I, 1015 Lausanne, Switzerland.
  • Nicolardi S Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
  • Paša-Tolić L Pacific Northwest National Laboratory, Richland, Washington 99354, United States.
  • Pengelley S Bruker Daltonik GmbH, 28359 Bremen, Germany.
  • Quebbemann NR University of California-Los Angeles, Los Angeles, California 90095, United States.
  • Resemann A Bruker Daltonik GmbH, 28359 Bremen, Germany.
  • Sandoval W Genentech, Inc., South San Francisco, California 94080-4990, United States.
  • Sarin R Biogen, Inc., Cambridge, Massachusetts 02142-1031, United States.
  • Schmitt ND Northeastern University, Boston, Massachusetts 02115, United States.
  • Shabanowitz J University of Virginia, Charlottesville, Virginia 22901, United States.
  • Shaw JB Pacific Northwest National Laboratory, Richland, Washington 99354, United States.
  • Shortreed MR University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
  • Smith LM University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
  • Sobott F University of Antwerp, 2000 Antwerp, Belgium.
  • Suckau D Bruker Daltonik GmbH, 28359 Bremen, Germany.
  • Toby T Northwestern University, Evanston, Illinois 60208-0001, United States.
  • Weisbrod CR National High Magnetic Field Laboratory, Tallahassee, Florida 32310, United States.
  • Wildburger NC Washington University School of Medicine, St. Louis, Missouri 63110, United States.
  • Yates JR The Scripps Research Institute, La Jolla, California 92037, United States.
  • Yoon SH University of Maryland, Baltimore, Maryland 21201, United States.
  • Young NL Baylor College of Medicine, Houston, Texas 77030-3411, United States.
  • Zhou M Pacific Northwest National Laboratory, Richland, Washington 99354, United States.
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  • 2020-08-20
Published in:
  • Journal of the American Society for Mass Spectrometry. - 2020
FTMS
Fourier transform mass spectrometry
MS/MS
Therapeutic protein
glycoform
intact mass measurement
tandem mass spectrometry
English The Consortium for Top-Down Proteomics (www.topdownproteomics.org) launched the present study to assess the current state of top-down mass spectrometry (TD MS) and middle-down mass spectrometry (MD MS) for characterizing monoclonal antibody (mAb) primary structures, including their modifications. To meet the needs of the rapidly growing therapeutic antibody market, it is important to develop analytical strategies to characterize the heterogeneity of a therapeutic product's primary structure accurately and reproducibly. The major objective of the present study is to determine whether current TD/MD MS technologies and protocols can add value to the more commonly employed bottom-up (BU) approaches with regard to confirming protein integrity, sequencing variable domains, avoiding artifacts, and revealing modifications and their locations. We also aim to gather information on the common TD/MD MS methods and practices in the field. A panel of three mAbs was selected and centrally provided to 20 laboratories worldwide for the analysis: Sigma mAb standard (SiLuLite), NIST mAb standard, and the therapeutic mAb Herceptin (trastuzumab). Various MS instrument platforms and ion dissociation techniques were employed. The present study confirms that TD/MD MS tools are available in laboratories worldwide and provide complementary information to the BU approach that can be crucial for comprehensive mAb characterization. The current limitations, as well as possible solutions to overcome them, are also outlined. A primary limitation revealed by the results of the present study is that the expert knowledge in both experiment and data analysis is indispensable to practice TD/MD MS.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/120713
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