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

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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