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Journal Articles Journal of The American Society for Mass Spectrometry Year : 2020

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

Kristina Srzentić
  • Function : Author
Luca Fornelli
  • Function : Author
Yury Tsybin
  • Function : Author
Joseph Loo
  • Function : Author
Henrique Seckler
  • Function : Author
Jeffrey Agar
  • Function : Author
Lissa Anderson
  • Function : Author
Dina Bai
  • Function : Author
Jennifer Brodbelt
  • Function : Author
Yuri van Der Burgt
  • Function : Author
Julia Chamot-Rooke
Sneha Chatterjee
  • Function : Author
Yunqiu Chen
  • Function : Author
David Clarke
  • Function : Author
Paul Danis
  • Function : Author
Jolene Diedrich
  • Function : Author
Robert D’ippolito
  • Function : Author
Mathieu Dupré
Natalia Gasilova
  • Function : Author
Ying Ge
  • Function : Author
Young Ah Goo
  • Function : Author
David Goodlett
  • Function : Author
Sylvester Greer
  • Function : Author
Kim Haselmann
  • Function : Author
Lidong He
  • Function : Author
Christopher Hendrickson
  • Function : Author
Joshua Hinkle
  • Function : Author
Matthew Holt
Sam Hughes
  • Function : Author
Donald Hunt
  • Function : Author
Neil Kelleher
  • Function : Author
Anton Kozhinov
  • Function : Author
Ziqing Lin
  • Function : Author
Christian Malosse
  • Function : Author
Alan Marshall
Laure Menin
  • Function : Author
Robert Millikin
  • Function : Author
Konstantin Nagornov
  • Function : Author
Simone Nicolardi
  • Function : Author
Ljiljana Paša-Tolić
  • Function : Author
Stuart Pengelley
  • Function : Author
Neil Quebbemann
  • Function : Author
Anja Resemann
  • Function : Author
Wendy Sandoval
  • Function : Author
Richa Sarin
  • Function : Author
Nicholas Schmitt
  • Function : Author
Jeffrey Shabanowitz
  • Function : Author
Jared Shaw
  • Function : Author
Michael Shortreed
  • Function : Author
Lloyd Smith
  • Function : Author
Frank Sobott
  • Function : Author
Detlev Suckau
  • Function : Author
Timothy Toby
  • Function : Author
Chad Weisbrod
Norelle Wildburger
  • Function : Author
John Yates
  • Function : Author
Sung Hwan Yoon
  • Function : Author
Nicolas Young
  • Function : Author
Mowei Zhou
  • Function : Author

Abstract

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.

Dates and versions

pasteur-03070508 , version 1 (15-12-2020)

Identifiers

Cite

Kristina Srzentić, Luca Fornelli, Yury Tsybin, Joseph Loo, Henrique Seckler, et al.. Interlaboratory Study for Characterizing Monoclonal Antibodies by Top-Down and Middle-Down Mass Spectrometry. Journal of The American Society for Mass Spectrometry, 2020, 31 (9), pp.1783-1802. ⟨10.1021/jasms.0c00036⟩. ⟨pasteur-03070508⟩

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