Klin Padiatr 2022; 234(03): 190-191
DOI: 10.1055/s-0042-1748751
Abstracts

High antileukemic efficiency of CD19-CAR NK cells engineered with Sleeping Beauty transposon vectors

Authors

  • T Bexte

    1   Experimental Immunology, Department for Children and Adolescents Medicine, Hospital of the Goethe University Frankfurt, 60590, Germany
    2   Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany
    3   University Cancer Center (UCT) Frankfurt-Marburg

  • L Botezatu

    4   Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany

  • C Miskey

    4   Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany

  • LM Reindl

    1   Experimental Immunology, Department for Children and Adolescents Medicine, Hospital of the Goethe University Frankfurt, 60590, Germany

  • J Campe

    1   Experimental Immunology, Department for Children and Adolescents Medicine, Hospital of the Goethe University Frankfurt, 60590, Germany

  • S Mertlitz

    5   Charité Universitätsmedizin Berlin, Berlin, Germany

  • V Gebel

    1   Experimental Immunology, Department for Children and Adolescents Medicine, Hospital of the Goethe University Frankfurt, 60590, Germany
    2   Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany
    3   University Cancer Center (UCT) Frankfurt-Marburg

  • R Schubert

    6   Department for Children and Adolescents, University Hospital, Goethe-University, Frankfurt, Germany

  • A Cremer

    7   Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany

  • E Rettinger

    8   Division of Stem Cell Transplantation and Immunology, Department of Children and Adolescent Medicine, Hospital of the Goethe University Frankfurt, 60590, Germany

  • S Prommersberger

    9   Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany

  • O Penack

    5   Charité Universitätsmedizin Berlin, Berlin, Germany

  • WS Wels

    2   Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany
    10   Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany
    11   German Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany

  • M Hudecek

    9   Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany

  • Z Ivics

    4   Division of Medical Biotechnology, Paul Ehrlich Institute, Langen, Germany

  • E Ullrich

    1   Experimental Immunology, Department for Children and Adolescents Medicine, Hospital of the Goethe University Frankfurt, 60590, Germany
    2   Frankfurt Cancer Institute, Goethe University, Frankfurt am Main, Germany
    3   University Cancer Center (UCT) Frankfurt-Marburg
    11   German Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany
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Expression of chimeric antigen receptors (CAR) constitutes a promising approach to enhance therapeutic efficacy of NK cells. Here, we demonstrate that primary CAR NK cells can be generated using the non-viral Sleeping Beauty (SB) transposon/transposase.

SB transposons vectorized as minicircles, encoding a CD19-CAR were transfected together with the hyperactive SB100X transposase. SB-modified NK cells displayed long-lasting CD19-CAR expression during ex-vivo expansion. Assessment of vector integration revealed a significantly higher frequency of insertion into genomic safe harbors for SB-CAR-NK cells compared to lentivirally-transduced CAR-NK cells. SB-CD19-CAR NK cells demonstrated significantly higher cytotoxicity compared to non-modified NK cells in vitro. Enhanced antitumor potential was confirmed in a systemic CD19-expressing leukemia xenograft model (NSG-NALM-6/Luc) in vivo. In addition, enhanced SB-CD19-CAR NK cell-mediated killing capacity was also observed against primary patient-derived B-ALL blasts.

The Sleeping Beauty transposon system represents a safe and cost-effective platform for CAR NK cells generation and can be suitable also for other cancer immunotherapies.


Publication History

Article published online:
17 May 2022

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