Evidence map›Paper›PMID 33843201›Full record

ArticleACS synthetic biology2021

Directed Evolution of Stabilized Monomeric CD19 for Monovalent CAR Interaction Studies and Monitoring of CAR-T Cell Patients.

Elisabeth Laurent, Anna Sieber, Benjamin Salzer, Anna Wachernig, Jacqueline Seigner, Manfred Lehner, René Geyeregger, Bernhard Kratzer, Ulrich Jäger, Renate Kunert and 2 more

Abstract read
In one paragraph

Article in ACS synthetic 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
–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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. The frequency of differentiated CD3Frontiers in immunology · 2022
    Article
  10. Affinity and Stability Analysis of Yeast Displayed Proteins.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  11. 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

12 authors.

Elisabeth LaurentDepartment of Biotechnology and BOKU Core Facility Biomolecular and Cellular Analysis, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.ORCID 0000-0002-5234-5524
Anna SieberDepartment of Biotechnology, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.
Benjamin SalzerSt. Anna Children's Cancer Research Institute, Zimmermannplatz 10, 1090 Vienna, Austria.
Anna WachernigDepartment of Biotechnology, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.
Jacqueline SeignerDepartment of Chemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.
Manfred LehnerSt. Anna Children's Cancer Research Institute, Zimmermannplatz 10, 1090 Vienna, Austria.
René GeyereggerSt. Anna Children's Cancer Research Institute, Zimmermannplatz 10, 1090 Vienna, Austria.
Bernhard KratzerInstitute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.
Ulrich JägerDepartment of Internal Medicine, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Renate KunertDepartment of Biotechnology, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.
Winfried F PicklInstitute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Lazarettgasse 19, 1090 Vienna, Austria.
Michael W TraxlmayrDepartment of Chemistry, BOKU - University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria.

Funding

Austrian Science Fund FWF W 1224
6 · The paper itself

Abstract

CD19 is among the most relevant targets in cancer immunotherapy. However, its extracellular domain (ECD) is prone to aggregation and misfolding, representing a major obstacle for the development and analysis of CD19-targeted therapeutics. Here, we engineered stabilized CD19-ECD (termed SuperFolder) variants, which also showed improved expression rates and, in contrast to the wild type protein, they could be efficiently purified in their monomeric forms. Despite being considerably more stable, these engineered mutants largely preserved the wild type sequence (>98.8%). We demonstrate that the variant SF05 enabled the determination of the monovalent affinity between CD19 and a clinically approved FMC63-based CAR, as well as monitoring and phenotypic characterization of CD19-directed CAR-T cells in the blood of lymphoma patients. We anticipate that the SuperFolder mutants generated in this study will be highly valuable tools for a range of applications in basic immunology and CD19-targeted cancer immunotherapy.

Indexed as

Amino Acid SubstitutionAmino AcidsAmino Acid SequenceAntibodies, MonoclonalAntigens, CD19Directed Molecular EvolutionHEK293 CellsHumansImmunotherapy, AdoptiveLymphoma, Large B-Cell, DiffuseMutant ProteinsMutationProtein DomainsProtein FoldingProtein StabilityReceptors, Chimeric AntigenAmino AcidsAntibodies, MonoclonalAntigens, CD19CD19 molecule, humanMutant ProteinsReceptors, Chimeric AntigenCD19chimeric antigen receptor (CAR)directed evolutionFMC63protein engineeringyeast surface display

Identifiers

PMID33843201
PMCPMC8155657

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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.