Evidence map›Paper›PMID 26601215›Full record

ArticleScience advances2015

Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase.

Kristen M Lorentz, Stephan Kontos, Giacomo Diaceri, Hugues Henry, Jeffrey A Hubbell

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 87 citations in OpenAlex.

  1. Review
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  4. Cell-drug conjugates.Nature biomedical engineering · 2024
    Review
  5. Enzyme Engineering Strategies for the Bioenhancement of L-Asparaginase Used as a Biopharmaceutical.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
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  14. An in vivo selection-derived d-peptide for engineering erythrocyte-binding antigens that promote immune tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Article
  16. Molecular therapy. Methods & clinical development · 2021
    Article
  17. Article
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  19. Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  20. Article
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

5 authors at 3 institutions in 2 countries.

Kristen M LorentzInstitute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. ; Anokion SA, CH-1024 Ecublens, Switzerland.
Stephan KontosInstitute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. ; Anokion SA, CH-1024 Ecublens, Switzerland.
Giacomo DiaceriInstitute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Hugues HenryCentre Hospitalier Universitaire Vaudois, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland.
Jeffrey A HubbellInstitute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. ; Anokion SA, CH-1024 Ecublens, Switzerland. ; Institute for Molecular Engineering, University of Chicago, Chicago, IL 60637, USA. ; Materials Science Division, Argonne National Laboratory, Argonne, IL 60439, USA.
École Polytechnique Fédérale de Lausanne · CHUniversity Hospital of Lausanne · CHUniversity of Chicago · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antigen-specific immune responses to protein drugs can hinder efficacy and compromise safety because of drug neutralization and secondary clinical complications. We report a tolerance induction strategy to prevent antigen-specific humoral immune responses to therapeutic proteins. Our modular, biomolecular approach involves engineering tolerizing variants of proteins such that they bind erythrocytes in vivo upon injection, on the basis of the premise that aged erythrocytes and the payloads they carry are cleared tolerogenically, driving the deletion of antigen-specific T cells. We demonstrate that binding the clinical therapeutic enzyme Escherichia coli l-asparaginase to erythrocytes in situ antigen-specifically abrogates development of antibody titers by >1000-fold and extends the pharmacodynamic effect of the drug 10-fold in mice. Additionally, a single pretreatment dose of erythrocyte-binding asparaginase tolerized mice to multiple subsequent doses of the wild-type enzyme. This strategy for reducing antigen-specific humoral responses may enable more effective and safer treatment with therapeutic proteins and drug candidates that are hampered by immunogenicity.

Indexed as

asparaginaseerythrocyteImmunological toleranceprotein drug

Identifiers

PMID26601215
PMCPMC4646778
OpenAlexW2249829928

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.