The Consortium for Top-Down Proteomics to Present Monoclonal Antibodies Study at ASMS 2017

Preliminary results from 25-laboratory study demonstrate the capabilities of top-down mass spectrometry for detailing monoclonal antibody structure and modifications. The presentation is Monday, June 5 at the Top-Down Proteomics Workshop at the ASMS Conference in Indianapolis, IN

CAMBRIDGE, MA–(Marketwired – May 31, 2017) – The Consortium for Top-Down Proteomics will present the preliminary results from their inter-laboratory study for characterizing monoclonal antibodies (mAbs) by top-down mass spectrometry techniques on June 5, 2017 at the upcoming American Society for Mass Spectrometry Annual Conference. With the continuing growth in the development and adoption of mAbs for a wide range of therapeutic uses, there is increasing demand for higher quality characterization of these complex species. This study is assessing the state of the art for providing critical information on these important materials.

The participants in this study utilized multiple workflows and have identified the major proteoforms of all three mAbs provided, as well as their relative abundances. In addition the six complementarity-determining regions (CDRs) in each of the mAbs, which are essential for their functions, were covered. Top-down MS/MS data provided structural information on all of them, with a combined result yielding up to 100% sequence coverage. Overall sequence coverage on the intact mAbs and their subunits averaged around 60-70%, based on results from multiple fragmentation methods.

“Though there is tremendous diversity in the analytical approaches taken, we are very pleased to see a good deal of consistency in the results,” remarked Yury Tsybin, of Spectroswiss Sarl and co-leader of the study. “The detailed information on the proteoforms and their modifications is vital and we are seeing strong supporting data,” added Joe Loo, co-leader of the study and Professor in the Department of Biological Chemistry, David Geffen School of Medicine, and in the Department of Chemistry & Biochemistry at the University of California, Los Angeles.

Researchers in the study were provided three monoclonal antibodies: Sigma SILu™ Lite mAb standard, NIST mAb standard, and a commercially available therapeutic mAb as well as the mAb subunits enzymatically prepared with Genovis’ IdeS/Fabricator® and KGP/GingisKHAN®. Researchers employed FT-ICR, QTOF, TOF/TOF, and Orbitrap instrumentation with ESI and MALDI sources, seven different fragmentation methods, and seven bioinformatics packages.

In addition to the Workshop, there will be Top-Down Poster Sessions on Monday, June 5 and Tuesday, June 6, as well as an oral session on Top-Down Proteomics on Thursday, June 8. Final results of this study will be published later this year.

About the Consortium for Top-Down Proteomics

The Consortium for Top-Down Proteomics is a non-profit organization fostering collaboration, education, and innovative research to accelerate the comprehensive analysis of intact proteins and their complexes, speeding developments in the fields of therapeutics, diagnostics, environment, and energy. It has members from academic institutions, corporations, and government agencies worldwide, and its work is supported by sponsorships from Thermo Fisher Scientific Inc., Bruker Daltonics, and Genovis AB.