Evidence map›Paper›PMID 37701441›Full record

ArticleFrontiers in immunology2023

Resistance to anti-PD-1/anti-PD-L1: galectin-3 inhibition with GB1211 reverses galectin-3-induced blockade of pembrolizumab and atezolizumab binding to PD-1/PD-L1.

Joseph Mabbitt, Ian D Holyer, James A Roper, Ulf J Nilsson, Fredrik R Zetterberg, Lynda Vuong, Alison C Mackinnon, Anders Pedersen, Robert J Slack

Abstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

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  16. Mechanisms of primary resistance to immune checkpoint inhibitors in NSCLC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
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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

9 authors.

Joseph MabbittStevenage Bioscience Catalyst, Galecto Biotech AB, Stevenage, United Kingdom.
Ian D HolyerNine Edinburgh BioQuarter, Galecto Biotech AB, Edinburgh, United Kingdom.
James A RoperStevenage Bioscience Catalyst, Galecto Biotech AB, Stevenage, United Kingdom.
Ulf J NilssonDepartment of Chemistry, Lund University, Lund, Sweden.
Fredrik R ZetterbergSahlgrenska Science Park, Galecto Biotech AB, Gothenburg, Sweden.
Lynda VuongDepartment of Surgery, Urology Service, Memorial Sloane Kettering Cancer Centre, New York, NY, United States.
Alison C MackinnonNine Edinburgh BioQuarter, Galecto Biotech AB, Edinburgh, United Kingdom.
Anders PedersenCobis Science Park, Galecto Biotech AB, Copenhagen, Denmark.
Robert J SlackStevenage Bioscience Catalyst, Galecto Biotech AB, Stevenage, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Galectin-3 (Gal-3) is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and has been suggested to predict a poor response to immune checkpoint therapy with the anti-PD-1 monoclonal antibody pembrolizumab. We aimed to assess if the effect of Gal-3 was a result of direct interaction with the immune checkpoint receptor. Methods: The ability of Gal-3 to interact with the PD-1/PD-L1 complex in the absence and presence of blocking antibodies was assessed in Results: Gal-3 reduced the binding of the checkpoint inhibitors pembrolizumab (anti-PD-1) and atezolizumab (anti-PD-L1), by potentiating the interaction between the PD-1/PD-L1 complex. In the presence of a highly selective Gal-3 small molecule inhibitor (GB1211) the binding of the anti-PD-1/anti-PD-L1 therapeutics was restored to control levels. This was observed in both a surface plasmon resonance assay measuring protein-protein interactions and Conclusion: Our study suggests that Gal-3 can potentiate the PD-1/PD-L1 immune axis and potentially contribute to the immunosuppressive signalling mechanisms within the tumor microenvironment. In addition, Gal-3 prevents atezolizumab and pembrolizumab target engagement with their respective immune checkpoint receptors. Reversal of this effect with the clinical candidate GB1211 offers a potential enhancing combination therapeutic with anti-PD-1 and -PD-L1 blocking antibodies.

Indexed as

Antibodies, Monoclonal, HumanizedGalectin 3AnimalsAntibodies, BlockingMiceAntibodies, BlockingAntibodies, Monoclonal, HumanizedatezolizumabGalectin 3pembrolizumabatezolizumabbindingcomputational chemistrygalectin-3 (Gal3)immuno-oncologyPD-1 - PDL-1 axispembrolizumab

Identifiers

PMID37701441
PMCPMC10493609

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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.