Evidence map›Paper›PMID 38653243›Full record

ArticleCell chemical biology2024

Facile generation of biepitopic antibodies with intrinsic agonism for activating tumor necrosis factor receptors.

Harkamal S Jhajj, John S Schardt, Namir Khalasawi, Emily L Yao, Timon S Lwo, Na-Young Kwon, Ryen L O'Meara, Alec A Desai, Peter M Tessier

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Harkamal S JhajjDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
John S SchardtDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Namir KhalasawiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Emily L YaoDepartment of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Timon S LwoDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Na-Young KwonDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Ryen L O'MearaDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Alec A DesaiDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Peter M TessierDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ptessier@umich.edu.
University of Michigan · US

Funding

CD98hc Brain Shuttles for Delivering Off-the-shelf Neuroprotective Antibodies in Alzheimer's DiseaseR01AG080016 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Colin Fred Greineder, Peter M Tessier · 2023 to 2026
$3.2M
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 R01 AG080016NIA NIH HHS RF1 AG059723NIGMS NIH HHS F32 GM137513NIGMS NIH HHS R35 GM136300
6 · The paper itself

Abstract

Agonist antibodies are being pursued for therapeutic applications ranging from neurodegenerative diseases to cancer. For the tumor necrosis factor (TNF) receptor superfamily, higher-order clustering of three or more receptors is key to their activation, which can be achieved using antibodies that recognize two unique epitopes. However, the generation of biepitopic (i.e., biparatopic) antibodies typically requires animal immunization and is laborious and unpredictable. Here, we report a simple method for identifying biepitopic antibodies that potently activate TNF receptors without the need for additional animal immunization. Our approach uses existing, receptor-specific IgGs, which lack intrinsic agonist activity, to block their corresponding epitopes, then selects single-chain antibodies that bind accessible epitopes. The selected antibodies are fused to the light chains of IgGs to generate human tetravalent antibodies. We highlight the broad utility of this approach by converting several clinical-stage antibodies against OX40 and CD137 (4-1BB) into biepitopic antibodies with potent agonist activity.

Indexed as

EpitopesAnimalsAntibodiesHumansMiceReceptors, OX40Receptors, Tumor Necrosis FactorSingle-Chain AntibodiesTumor Necrosis Factor Receptor Superfamily, Member 9AntibodiesEpitopesReceptors, OX40Receptors, Tumor Necrosis FactorSingle-Chain AntibodiesTumor Necrosis Factor Receptor Superfamily, Member 94-1BBagonistantibodybiparatopicCD137FcγRmAbOX40receptor clusteringTNFTNFR

Identifiers

PMID38653243
PMCPMC11142405
OpenAlexW4394998594

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.