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DOI: 10.1055/s-0042-1748751
High antileukemic efficiency of CD19-CAR NK cells engineered with Sleeping Beauty transposon vectors
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.
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Publication History
Article published online:
17 May 2022
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