Evidence map›Paper›PMID 39180756›Full record

ReviewmAbs

The emergence of cell-based protein arrays to test for polyspecific off-target binding of antibody therapeutics.

Diana M Norden, Carmen T Navia, Jonathan T Sullivan, Benjamin J Doranz

Abstract readReview
In one paragraph

Review in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  7. 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

4 authors.

Diana M NordenIntegral Molecular, Philadelphia, PA, USA.
Carmen T NaviaIntegral Molecular, Philadelphia, PA, USA.
Jonathan T SullivanIntegral Molecular, Philadelphia, PA, USA.
Benjamin J DoranzIntegral Molecular, Philadelphia, PA, USA.

Funding

Next Generation Specificity Screening for Biotherapeutics using an Extracellular Proteome ArrayR44GM113556 · NIGMS · INTEGRAL MOLECULAR · PI DORANZ, BENJAMIN J · 2017 to 2022
$3.2M
High-throughput Identification of Membrane Protein MAbsR43GM113556 · NIGMS · INTEGRAL MOLECULAR · PI DORANZ, BENJAMIN J · 2015 to 2015
$225k
NIGMS NIH HHS R43 GM113556NIGMS NIH HHS R44 GM113556
6 · The paper itself

Abstract

Specificity profiling is a requirement for monoclonal antibodies (mAbs) and antibody-directed biotherapeutics such as CAR-T cells prior to initiating human trials. However, traditional approaches to assess the specificity of mAbs, primarily tissue cross-reactivity studies, have been unreliable, leading to off-target binding going undetected. Here, we review the emergence of cell-based protein arrays as an alternative and improved assessment of mAb specificity. Cell-based protein arrays assess binding across the full human membrane proteome, ~6,000 membrane proteins each individually expressed in their native structural configuration within live or unfixed cells. Our own profiling indicates a surprisingly high off-target rate across the industry, with 33% of lead candidates displaying off-target binding. Moreover, about 20% of therapeutic mAbs in clinical development and currently on the market display off-target binding. Case studies and off-target rates at different phases of biotherapeutic drug approval suggest that off-target binding is likely a major cause of adverse events and drug attrition.

Indexed as

Antibodies, MonoclonalProtein Array AnalysisAnimalsAntibody SpecificityHumansProtein BindingAntibodies, MonoclonalAntibodycell-based protein arraycross-reactivitymembrane proteome arrayoff-target bindingpolyspecificitysafetyspecificity

Identifiers

PMID39180756
PMCPMC11346545

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.