Evidence map›Paper›PMID 37244165›Full record

ArticleJournal of chromatography. A2023

Behavior of host-cell-protein-rich aggregates in antibody capture and polishing chromatography.

Chase E Herman, Lie Min, Leila H Choe, Ronald W Maurer, Xuankuo Xu, Sanchayita Ghose, Kelvin H Lee, Abraham M Lenhoff

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of chromatography. A, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
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

8 authors.

Chase E HermanDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.
Lie MinDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.
Leila H ChoeDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.
Ronald W MaurerBiologics Development, Bristol Myers Squibb, Devens, MA 01434, USA.
Xuankuo XuBiologics Development, Bristol Myers Squibb, Devens, MA 01434, USA.
Sanchayita GhoseBiologics Development, Bristol Myers Squibb, Devens, MA 01434, USA.
Kelvin H LeeDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA.
Abraham M LenhoffDepartment of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, USA. Electronic address: lenhoff@udel.edu.

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI MELINDA K DUNCAN · 2012 to 2026
$67.2M
Understanding synovial macrophage inflamm-aging within osteoarthritisP20GM139760 · NIGMS · UNIVERSITY OF DELAWARE · PI DAWN M ELLIOTT · 2021 to 2026
$19.1M
Zeiss LSM710 Inverted Confocal MicroscopeS10OD016361 · OD · UNIVERSITY OF DELAWARE · PI CAPLAN, JEFFREY L · 2015 to 2015
$444k
NIGMS NIH HHS P20 GM103446NIGMS NIH HHS P20 GM139760NIH HHS S10 OD016361
6 · The paper itself

Abstract

Recent work has shown that aggregates in monoclonal antibody (mAb) solutions may be made up not just of mAb oligomers but can also harbor hundreds of host-cell proteins (HCPs), suggesting that aggregate persistence through downstream purification operations may be related to HCP clearance. We have examined this in a primary analysis of aggregate persistence through processing steps that are typically implemented for HCP reduction, demonstrating that the phenomenon is relevant to depth filtration, protein A chromatography and flow-through anion-exchange (AEX) polishing. Confocal laser scanning microscopy observations show that aggregates compete with the mAb to adsorb specifically in protein A chromatography and that this competitive interaction is integral to the efficacy of protein A washes. Column chromatography reveals that the protein A elution tail can have a relatively high concentration of aggregates, which corroborates analogous observations from recent HCP studies. Similar measurements in flow-through AEX chromatography show that relatively large aggregates that harbor HCPs and that persist into the protein A eluate can be retained to an extent that appears to depend primarily on the resin surface chemistry. The total aggregate mass fraction of both protein A eluate pools (∼ 2.4 - 3.6%) and AEX flow-through fractions (∼ 1.5 - 3.2%) correlates generally with HCP concentrations measured using enzyme-linked immunosorbent assay (ELISA) as well as the number of HCPs that may be identified in proteomic analysis. This suggests that quantification of the aggregate mass fraction may serve as a convenient albeit imperfect surrogate for informing early process development decisions regarding HCP clearance strategies.

Indexed as

ChromatographyProteomicsAnimalsAnionsAntibodies, MonoclonalCHO CellsCricetinaeCricetulusStaphylococcal Protein AAnionsAntibodies, MonoclonalStaphylococcal Protein AAggregateAnion-exchangeHost-cell proteinProtein A chromatographyProteomics

Identifiers

PMID37244165
PMCPMC10299761

What OpenQuestion holds

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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.