Evidence map›Paper›PMID 34258999›Full record

ArticleAnalytical chemistry2021

High-Throughput Multi-attribute Analysis of Antibody-Drug Conjugates Enabled by Trapped Ion Mobility Spectrometry and Top-Down Mass Spectrometry.

Eli J Larson, David S Roberts, Jake A Melby, Kevin M Buck, Yanlong Zhu, Shiyue Zhou, Linjie Han, Qunying Zhang, Ying Ge

Open access · greenAbstract read
In one paragraph

Article in Analytical chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Top-Down and Middle-Down Mass Spectrometry of Antibodies.Molecular & cellular proteomics : MCP · 2025
    Review
  5. Mobility-Assisted Pseudo-MSJournal of the American Society for Mass Spectrometry · 2024
    Article
  6. Evaluation of a Commercial TIMS-Q-TOF Platform for Native Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Enhancing the Depth of Analyses with Next-Generation Ion Mobility Experiments.Annual review of analytical chemistry (Palo Alto, Calif.) · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Eli J LarsonDepartment of Chemistry, University of Wisconsin - Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.ORCID 0000-0002-1354-0722
David S RobertsDepartment of Chemistry, University of Wisconsin - Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.ORCID 0000-0002-0478-4987
Jake A MelbyDepartment of Chemistry, University of Wisconsin - Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.ORCID 0000-0003-1499-9508
Kevin M BuckDepartment of Chemistry, University of Wisconsin - Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
Yanlong ZhuDepartment of Cell and Regenerative Biology, University of Wisconsin - Madison, 1111 Highland Avenue., Madison, Wisconsin 53705, United States.ORCID 0000-0003-4909-7336
Shiyue ZhouAnalytical R&D, AbbVie Inc., 1 Waukegan Rd, North Chicago, Illinois 60064, United States.
Linjie HanAnalytical R&D, AbbVie Inc., 1 Waukegan Rd, North Chicago, Illinois 60064, United States.
Qunying ZhangAnalytical R&D, AbbVie Inc., 1 Waukegan Rd, North Chicago, Illinois 60064, United States.
Ying GeDepartment of Chemistry, University of Wisconsin - Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.ORCID 0000-0001-5211-6812
University of Wisconsin–Madison · USAbbVie (United States) · US

Funding

Training Program in Translational Cardiovascular Science (TPTCS)T32HL007936 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI Lee Lochbaum Eckhardt, Gail A Robertson · 2001 to 2026
$11.6M
Enabling Top-Down Proteomics through Materials Chemistry and NanotechnologyR01GM117058 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING, JIN, SONG · 2015 to 2023
$2.7M
MASH Explorer, a Comprehensive Software Environment for Top-Down ProteomicsR01GM125085 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GE, YING · 2018 to 2021
$1.2M
NHLBI NIH HHS T32 HL007936NIGMS NIH HHS R01 GM117058NIGMS NIH HHS R01 GM125085
6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) are one of the fastest growing classes of anticancer therapies. Combining the high targeting specificity of monoclonal antibodies (mAbs) with cytotoxic small molecule drugs, ADCs are complex molecular entities that are intrinsically heterogeneous. Primary sequence variants, varied drug-to-antibody ratio (DAR) species, and conformational changes in the starting mAb structure upon drug conjugation must be monitored to ensure the safety and efficacy of ADCs. Herein, we have developed a high-throughput method for the analysis of cysteine-linked ADCs using trapped ion mobility spectrometry (TIMS) combined with top-down mass spectrometry (MS) on a Bruker timsTOF Pro. This method can analyze ADCs (∼150 kDa) by TIMS followed by a three-tiered top-down MS characterization strategy for multi-attribute analysis. First, the charge state distribution and DAR value of the ADC are monitored (MS1). Second, the intact mass of subunits dissociated from the ADC by low-energy collision-induced dissociation (CID) is determined (MS2). Third, the primary sequence for the dissociated subunits is characterized by CID fragmentation using elevated collisional energies (MS3). We further automate this workflow by directly injecting the ADC and using MS segmentation to obtain all three tiers of MS information in a single 3-min run. Overall, this work highlights a multi-attribute top-down MS characterization method that possesses unparalleled speed for high-throughput characterization of ADCs.

Indexed as

Antineoplastic AgentsImmunoconjugatesAntibodies, MonoclonalIon Mobility SpectrometryMass SpectrometryAntibodies, MonoclonalAntineoplastic AgentsImmunoconjugates

Identifiers

PMID34258999
PMCPMC8319120
OpenAlexW3180598267

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.