Evidence map›Paper›PMID 37666923›Full record

ArticleNature biomedical engineering2024

Optimization of therapeutic antibodies for reduced self-association and non-specific binding via interpretable machine learning.

Emily K Makowski, Tiexin Wang, Jennifer M Zupancic, Jie Huang, Lina Wu, John S Schardt, Anne S De Groot, Stephanie L Elkins, William D Martin, Peter M Tessier

Open access · greenAbstract read
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
8.9field-weighted citation impact, top 2% 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

32 citing papers in PubMed, 39 citations in OpenAlex.

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  8. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  20. Antibody-Nanoparticle Conjugates in Therapy: Combining the Best of Two Worlds.Small (Weinheim an der Bergstrasse, Germany) · 2025
    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

10 authors at 3 institutions in 1 country.

Emily K MakowskiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9709-9873
Tiexin WangBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Jennifer M ZupancicBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
Jie HuangDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.
Lina WuBiointerfaces Institute, University of Michigan, Ann Arbor, MI, USA.
John S SchardtDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA.
Anne S De GrootUniversity of Georgia, Athens, GA, USA.
Stephanie L ElkinsEpiVax, Inc., Providence, RI, USA.
William D MartinEpiVax, Inc., Providence, RI, USA.
Peter M TessierDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA. ptessier@umich.edu.ORCID http://orcid.org/0000-0002-3220-007X
University of Michigan · USProvidence College · USUniversity of Georgia · US

Funding

Interdepartmental Training in Pharmacological SciencesT32GM140223 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Lori L. Isom · 2021 to 2026
$3.8M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
Design and Evolution of Polyvalent Domain Antibodies Specific for Tau AggregatesRF1AG059723 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KANE, RAVI S., TESSIER, PETER M · 2018 to 2022
$2.4M
Structure-guided antibody targeting of pre-selected epitopes in amyloidogenic aggregatesR35GM136300 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESSIER, PETER M · 2020 to 2024
$1.5M
Administrative Supplement: Activity-based Discovery and OptimizationF32GM137513 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCHARDT, JOHN SAMUEL · 2020 to 2022
$141k
NIA NIH HHS RF1 AG059723NIGMS NIH HHS F32 GM137513NIGMS NIH HHS R35 GM136300NIGMS NIH HHS T32 GM140223NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

Antibody development, delivery, and efficacy are influenced by antibody-antigen affinity interactions, off-target interactions that reduce antibody bioavailability and pharmacokinetics, and repulsive self-interactions that increase the stability of concentrated antibody formulations and reduce their corresponding viscosity. Yet identifying antibody variants with optimal combinations of these three types of interactions is challenging. Here we show that interpretable machine-learning classifiers, leveraging antibody structural features descriptive of their variable regions and trained on experimental data for a panel of 80 clinical-stage monoclonal antibodies, can identify antibodies with optimal combinations of low off-target binding in a common physiological-solution condition and low self-association in a common antibody-formulation condition. For three clinical-stage antibodies with suboptimal combinations of off-target binding and self-association, the classifiers predicted variable-region mutations that optimized non-affinity interactions while maintaining high-affinity antibody-antigen interactions. Interpretable machine-learning models may facilitate the optimization of antibody candidates for therapeutic applications.

Indexed as

Antibodies, MonoclonalAntigensAntibody AffinityMachine LearningMutationAntibodies, MonoclonalAntigens

Identifiers

PMID37666923
PMCPMC10842909
OpenAlexW4386423687

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.