Evidence map›Paper›PMID 34119488›Full record

ArticleJournal of molecular biology2021

Biomolecular Recognition of the Glycan Neoantigen CA19-9 by Distinct Antibodies.

Aliza Borenstein-Katz, Shira Warszawski, Ron Amon, Maayan Eilon, Hadas Cohen-Dvashi, Shani Leviatan Ben-Arye, Nova Tasnima, Hai Yu, Xi Chen, Vered Padler-Karavani and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.7field-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

11 citing papers in PubMed, 20 citations in OpenAlex.

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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

12 authors at 3 institutions in 2 countries.

Aliza Borenstein-KatzDepartment of Chemical and Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Shira WarszawskiDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
Ron AmonDepartment of Cell Research and Immunology, The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Maayan EilonDepartment of Chemical and Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Hadas Cohen-DvashiDepartment of Chemical and Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Shani Leviatan Ben-AryeDepartment of Cell Research and Immunology, The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Nova TasnimaDepartment of Chemistry, University of California, Davis, CA 95616, USA.
Hai YuDepartment of Chemistry, University of California, Davis, CA 95616, USA.
Xi ChenDepartment of Chemistry, University of California, Davis, CA 95616, USA.
Vered Padler-KaravaniDepartment of Cell Research and Immunology, The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: vkaravani@tauex.tau.ac.il.
Sarel Jacob FleishmanDepartment of Biomolecular Sciences, Weizmann Institute of Science, 76100 Rehovot, Israel.
Ron DiskinDepartment of Chemical and Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel. Electronic address: ron.diskin@weizmann.ac.il.
Weizmann Institute of Science · ILTel Aviv University · ILUniversity of California, Davis · US

Funding

European Research Council 716220European Research Council 815379
6 · The paper itself

Abstract

Glycans decorate the cell surface, secreted glycoproteins and glycolipids, and altered glycans are often found in cancers. Despite their high diagnostic and therapeutic potential, however, glycans are polar and flexible molecules that are quite challenging for the development and design of high-affinity binding antibodies. To understand the mechanisms by which glycan neoantigens are specifically recognized by antibodies, we analyze the biomolecular recognition of the tumor-associated carbohydrate antigen CA19-9 by two distinct antibodies using X-ray crystallography. Despite the potential plasticity of glycans and the very different antigen-binding surfaces presented by the antibodies, both structures reveal an essentially identical extended CA19-9 conformer, suggesting that this conformer's stability selects the antibodies. Starting from the bound structure of one of the antibodies, we use the AbLIFT computational algorithm to design a variant with seven core mutations in the variable domain's light-heavy chain interface that exhibits tenfold improved affinity for CA19-9. The results reveal strategies used by antibodies to specifically recognize glycan antigens and show how automated antibody-optimization methods may be used to enhance the clinical potential of existing antibodies.

Indexed as

AlgorithmsAnimalsAntibodies, MonoclonalAntibody AffinityCA-19-9 AntigenComputational BiologyCrystallography, X-RayHumansMiceModels, MolecularMutationProtein ConformationAntibodies, MonoclonalCA-19-9 AntigenantibodiesCA19-9designglycansstructure

Identifiers

PMID34119488
PMCPMC7611348
OpenAlexW3169267749

What OpenQuestion holds

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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.