Evidence map›Paper›PMID 37300381›Full record

ArticleBiotechnology journal2023

Generation of IL-2-Fc-antibody conjugates by click chemistry.

Lindsay Williams, Lin Li, Paul J Yazaki, Patty Wong, Aaron Miller, Teresa Hong, Erasmus K Poku, Supriyo Bhattacharya, John E Shively, Maciej Kujawski

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

Article in Biotechnology journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.1field-weighted citation impact, top 22% 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, 5 citations in OpenAlex.

  1. Review
  2. 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

10 authors at 1 institution in 1 country.

Lindsay WilliamsDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.ORCID https://orcid.org/0000-0002-9877-2935
Lin LiDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.
Paul J YazakiDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.
Patty WongDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.
Aaron MillerDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.
Teresa HongDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.
Erasmus K PokuRadiopharmacy, City of Hope, Beckman Research Institute of City of Hope, Duarte, California, USA.
Supriyo BhattacharyaDepartment of Computational and Quantitative Medicine, Beckman Research Institute of City of Hope, Duarte, California, USA.ORCID https://orcid.org/0000-0003-0483-2149
John E ShivelyDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.ORCID https://orcid.org/0000-0002-7763-770X
Maciej KujawskiDepartment of Immunology and Theranostics, Riggs Diabetes, Metabolism, and Research Institute, Beckman Research Institute of City of Hope, Duarte, California, USA.ORCID https://orcid.org/0000-0002-9701-5211
City Of Hope National Medical Center · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
NCI NIH HHS P30 CA033572
6 · The paper itself

Abstract

backgroundImmunocytokines (ICKs) are antibody directed cytokines produced by genetic fusion of an antibody to a cytokine.

methodsWe now show that antibodies conjugated by click chemistry to interleukin-2 (IL-2)-Fc form fully active conjugates, and in one example, equivalent activity to a genetically produced ICK.

resultsAn IL-2-Fc fusion protein was optimized for click chemistry at hinge cysteines using protein stabilizing IL-2 mutations at Lys35 and Cys125 and Fc hinge mutations at Cys142 and Cys148. The IL-2-Fc fusion protein with K35E and C125S mutations with 3 intact hinge cysteines, designated as IL-2-Fc Par, was selected based on its minimal tendency to aggregate. IL-2-Fc-antibody clicked conjugates retained high IL-2 activity and bound target antigens comparable to parent antibodies. An IL-2-Fc-anti-CEA click conjugate showed comparable anti-tumor activity to an anti-CEA-IL-2 ICK in immunocompetent CEA transgenic mice bearing CEA positive orthotopic breast tumors. Significant increases in IFNγ

conclusionThe production of antibody targeted IL-2 therapy via a click chemistry approach is feasible with comparable activity to genetically produced ICKs with the added advantage of multiplexing with other monoclonal antibodies.

Indexed as

Interleukin-2NeoplasmsAnimalsAntibodies, MonoclonalClick ChemistryImmunoglobulin Fc FragmentsImmunotherapyMiceAntibodies, MonoclonalImmunoglobulin Fc FragmentsInterleukin-2carcinoembryonic antigenclick chemistryIL-2-Fcimmunocytokineimmunotherapy

Identifiers

PMID37300381
PMCPMC13682640
OpenAlexW4380153374

What OpenQuestion holds

Textmetadata
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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.