Evidence map›Paper›PMID 39271690›Full record

ArticleScientific reports2024

Label-free assessment of complement-dependent cytotoxicity of therapeutic antibodies via a whole-cell MALDI mass spectrometry bioassay.

Stefan Schmidt, Alexander Geisel, Thomas Enzlein, Björn C Fröhlich, Louise Pritchett, Melanie Verneret, Christian Graf, Carsten Hopf

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Stefan Schmidt *Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany.
Alexander Geisel *Center for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany.
Thomas EnzleinCenter for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany.
Björn C FröhlichCenter for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany.
Louise PritchettNovartis Pharma AG, Technical Research & Development Biologics, Klybeckstr. 141, 4056, Basel, Switzerland.
Melanie VerneretNovartis Pharma AG, Technical Research & Development Biologics, Klybeckstr. 141, 4056, Basel, Switzerland.
Christian GrafNovartis Business Services GmbH, Technical Research & Development Biologics, Oskar-von-Miller-Ring 33, 80333, München, Germany.
Carsten HopfCenter for Mass Spectrometry and Optical Spectroscopy (CeMOS), Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163, Mannheim, Germany. c.hopf@hs-mannheim.de.

Funding

Bundesministerium für Bildung und Forschung 16LW0238Hector Stiftung II MALDI-TOF MSMinisterium für Wissenschaft, Forschung und Kunst Baden-Württemberg MWK Mittelbauprogramm
6 · The paper itself

Abstract

Potency assessment of monoclonal antibodies or corresponding biosimilars in cell-based assays is an essential prerequisite in biopharmaceutical research and development. However, cellular bioassays are still subject to limitations in sample throughput, speed, and often need costly reagents or labels as they are based on an indirect readout by luminescence or fluorescence. In contrast, whole-cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry (MS) has emerged as a direct, fast and label-free technology for functional drug screening being able to unravel the molecular complexity of cellular response to pharmaceutical reagents. However, this approach has not yet been used for cellular testing of biologicals. In this study, we have conceived, developed and benchmarked a label-free MALDI-MS based cell bioassay workflow for the functional assessment of complement-dependent cytotoxicity (CDC) of Rituximab antibody. By computational evaluation of response profiles followed by subsequent m/z feature annotation via fragmentation analysis and trapped ion mobility MS, we identified adenosine triphosphate and glutathione as readily MS-assessable metabolite markers for CDC and demonstrate that robust concentration-response characteristics can be obtained by MALDI-TOF MS. Statistical assay performance indicators suggest that whole-cell MALDI-TOF MS could complement the toolbox for functional cellular testing of biopharmaceuticals.

Indexed as

RituximabSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationAdenosine TriphosphateAntibodies, MonoclonalBiological AssayComplement System ProteinsGlutathioneHumansAdenosine TriphosphateAntibodies, MonoclonalComplement System ProteinsGlutathioneRituximabComplement-dependent cytotoxicityDrug-response curvesLabel-free cell assayMALDIMass spectrometryMonoclonal antibody

Identifiers

PMID39271690
PMCPMC11399240

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Registered trials

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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.