Evidence map›Paper›PMID 38547863›Full record

ArticleCell chemical biology2024

Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.

Seth D Ludwig, Bunyarit Meksiriporn, Jiacheng Tan, Rakeeb Kureshi, Akhilesh Mishra, Kyle J Kaeo, Angela Zhu, Georgia Stavrakis, Stephen J Lee, David J Schodt and 7 more

Erratum issuedOpen 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. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Induced proximity at the cell surface.Nature biotechnology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Seth D LudwigDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Bunyarit MeksiripornDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biology, School of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand.
Jiacheng TanDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rakeeb KureshiDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Akhilesh MishraDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Kyle J KaeoDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Angela ZhuDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Georgia StavrakisDepartment of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA.
Stephen J LeeDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
David J SchodtDepartment of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131, USA.
Michael J WesterDepartment of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131, USA.
Dhiraj KumarDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Keith A LidkeDepartment of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131, USA.
Andrea L CoxDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Helen M DooleyDepartment of Microbiology and Immunology, Institute of Marine and Environmental Technology (IMET), University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Sridhar NimmagaddaDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Jamie B SpanglerDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: jamie.spangler@jhu.edu.
Johns Hopkins University · USUniversity of New Mexico · USBloomberg (United States) · USUniversity of Maryland, Baltimore · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI JEFFREY MUMM · 1985 to 2026
$22.1M
Clinical translation of a PD-L1 PET tracer to optimize immune checkpoint therapy in patients with non-small cell lung cancersR01CA269235 · NCI · JOHNS HOPKINS UNIVERSITY · PI Sridhar Nimmagadda, STEVEN P ROWE · 2022 to 2026
$3.2M
Non-invasive Quantification of Dose-Exposure-Response of PD-L1 Therapeutics at the TumorR01CA236616 · NCI · JOHNS HOPKINS UNIVERSITY · PI NIMMAGADDA, SRIDHAR · 2018 to 2022
$2.3M
OPTIMIZING THE PRE-CLINICAL DEVELOPMENT OF IMMUNOTHERAPEUTIC ANTIBODIES THROUGH GLYCOENGINEERINGR21CA249381 · NCI · JOHNS HOPKINS UNIVERSITY · PI SPANGLER, JAMIE BERTA, YAREMA, KEVIN J · 2020 to 2021
$410k
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA236616NCI NIH HHS R01 CA269235NCI NIH HHS R21 CA249381NEI NIH HHS P30 EY001765
6 · The paper itself

Abstract

Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance. Here, we report the development of antibody fusion proteins that block immune checkpoint pathways through a distinct mechanism targeting molecular trafficking. By engaging multiple receptor epitopes on PD-L1, our engineered multiparatopic antibodies induce rapid clustering, internalization, and degradation in an epitope- and topology-dependent manner. The complementary mechanisms of ligand blockade and receptor downregulation led to more durable immune cell activation and dramatically reduced PD-L1 availability in mouse tumors. Collectively, these multiparatopic antibodies offer mechanistic insight into immune checkpoint protein trafficking and how it may be manipulated to reprogram immune outcomes.

Indexed as

B7-H1 AntigenDown-RegulationAnimalsCell Line, TumorFemaleHumansMiceMice, Inbred C57BLTumor MicroenvironmentB7-H1 AntigenCD274 protein, humanantibodycancerdownregulationimmune checkpoint blockadeimmunotherapymolecular traffickingmultispecificPD-L1

Identifiers

PMID38547863
PMCPMC11102303
OpenAlexW4393237652

What OpenQuestion holds

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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.