Evidence map›Paper›PMID 38751112›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Engineering of potent CAR NK cells using non-viral Sleeping Beauty transposition from minimalistic DNA vectors.

Tobias Bexte, Lacramioara Botezatu, Csaba Miskey, Fenja Gierschek, Alina Moter, Philipp Wendel, Lisa Marie Reindl, Julia Campe, Jose Francisco Villena-Ossa, Veronika Gebel and 7 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

37 citing papers in PubMed.

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  11. Development andFrontiers in immunology · 2026
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  16. Restoring NK Cell Cytotoxicity Post-Cryopreservation via Synthetic Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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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

17 authors.

Tobias BexteGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany; University Cancer Center (UCT) Frankfurt, Frankfurt, Germany; Mildred Scheel Career Center (MSNZ), Hospital of the Goethe University Frankfurt, Frankfurt, Germany; Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Service Baden-Württemberg - Hesse, Frankfurt, Germany.
Lacramioara BotezatuResearch Centre, Division of Hematology, Gene and Cell Therapy, Paul-Ehrlich-Institut, Langen, Germany; German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany.
Csaba MiskeyResearch Centre, Division of Hematology, Gene and Cell Therapy, Paul-Ehrlich-Institut, Langen, Germany.
Fenja GierschekGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.
Alina MoterGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.
Philipp WendelGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, Germany.
Lisa Marie ReindlGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.
Julia CampeGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany.
Jose Francisco Villena-OssaInstitute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Freiburg, Germany.
Veronika GebelGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany; University Cancer Center (UCT) Frankfurt, Frankfurt, Germany; Mildred Scheel Career Center (MSNZ), Hospital of the Goethe University Frankfurt, Frankfurt, Germany.
Katja SteinGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany; University Cancer Center (UCT) Frankfurt, Frankfurt, Germany.
Toni CathomenInstitute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), partner site Freiburg, Freiburg, Germany.
Anjali CremerFrankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany; University Cancer Center (UCT) Frankfurt, Frankfurt, Germany; Mildred Scheel Career Center (MSNZ), Hospital of the Goethe University Frankfurt, Frankfurt, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Hematology/Oncology, University Hospital Frankfurt, Frankfurt am Main, Germany.
Winfried S WelsFrankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.
Michael HudecekDepartment of Medicine II, Chaire in Cellular Immunotherapy, University Hospital Würzburg, Würzburg, Germany; Fraunhofer Institute for Cell Therapy and Immunology, Cellular Immunotherapy Branch Site Würzburg, Würzburg, Germany.
Zoltán IvicsResearch Centre, Division of Hematology, Gene and Cell Therapy, Paul-Ehrlich-Institut, Langen, Germany; German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany.
Evelyn UllrichGoethe University, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany; Frankfurt Cancer Institute (FCI), Goethe University, Frankfurt am Main, Germany; University Cancer Center (UCT) Frankfurt, Frankfurt, Germany; Mildred Scheel Career Center (MSNZ), Hospital of the Goethe University Frankfurt, Frankfurt, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: evelyn@ullrichlab.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Natural killer (NK) cells have high intrinsic cytotoxic capacity, and clinical trials have demonstrated their safety and efficacy for adoptive cancer therapy. Expression of chimeric antigen receptors (CARs) enhances NK cell target specificity, with these cells applicable as off-the-shelf products generated from allogeneic donors. Here, we present for the first time an innovative approach for CAR NK cell engineering employing a non-viral Sleeping Beauty (SB) transposon/transposase-based system and minimized DNA vectors termed minicircles. SB-modified peripheral blood-derived primary NK cells displayed high and stable CAR expression and more frequent vector integration into genomic safe harbors than lentiviral vectors. Importantly, SB-generated CAR NK cells demonstrated enhanced cytotoxicity compared with non-transfected NK cells. A strong antileukemic potential was confirmed using established acute lymphocytic leukemia cells and patient-derived primary acute B cell leukemia and lymphoma samples as targets in vitro and in vivo in a xenograft leukemia mouse model. Our data suggest that the SB-transposon system is an efficient, safe, and cost-effective approach to non-viral engineering of highly functional CAR NK cells, which may be suitable for cancer immunotherapy of leukemia as well as many other malignancies.

Indexed as

Genetic VectorsImmunotherapy, AdoptiveKiller Cells, NaturalReceptors, Chimeric AntigenAnimalsCell EngineeringCell Line, TumorCytotoxicity, ImmunologicDNA Transposable ElementsHumansMicePrecursor Cell Lymphoblastic Leukemia-LymphomaTransposasesXenograft Model Antitumor AssaysDNA Transposable ElementsReceptors, Chimeric Antigensleeping beauty transposase, humanTransposasesacute lymphoblastic leukemiaallogenicCARCD19NK cellsnon-viralSleeping Beautytransposon

Identifiers

PMID38751112
PMCPMC11287004

What OpenQuestion holds

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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.