2009
DOI: 10.1038/cgt.2009.61
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Expression of chimeric antigen receptors in natural killer cells with a regulatory-compliant non-viral method

Abstract: Natural killer (NK) cells hold promise for cancer therapy. NK cytotoxicity can be enhanced by expression of chimeric antigen receptors that re-direct specificity toward target cells by engaging cell surface molecules expressed on target cells. We developed a regulatory-compliant, scalable non-viral approach to engineer NK cells to be target-specific based on transfection of mRNA encoding chimeric receptors. Transfection of eGFP mRNA into ex vivo expanded NK cells (N ¼ 5) or purified unstimulated NK cells from … Show more

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Cited by 126 publications
(109 citation statements)
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“…1A and data not shown). This prolonged high transgene persistence was different from most reports of peak and duration of expression of a surface antigen after mRNA transfection (Birkholz et al, 2009;Rabinovich et al, 2009;Yoon et al, 2009;Li et al, 2010), possibly due to our optimized IVT vector and RNA production (data not shown). In parallel, we assessed the cytotoxic potential of CAR-expressing T cells in vitro with a flow cytometry-based killing assay.…”
Section: Generation Of Car-expressing T Cells By Mrna Transfection Recontrasting
confidence: 99%
See 1 more Smart Citation
“…1A and data not shown). This prolonged high transgene persistence was different from most reports of peak and duration of expression of a surface antigen after mRNA transfection (Birkholz et al, 2009;Rabinovich et al, 2009;Yoon et al, 2009;Li et al, 2010), possibly due to our optimized IVT vector and RNA production (data not shown). In parallel, we assessed the cytotoxic potential of CAR-expressing T cells in vitro with a flow cytometry-based killing assay.…”
Section: Generation Of Car-expressing T Cells By Mrna Transfection Recontrasting
confidence: 99%
“…However, the improving technology for RNA transfection may complement the use of CARs that are stably expressed by integrating viral vector or transposon systems. A previous report demonstrated the feasibility of the mRNA transfection approach, achieving expression of a CD19 chimeric receptor in a natural killer cell line (Li et al, 2010). RNA CAR + CTLs targeted against solid-tumor antigens have also been reported, but only in the context of intratumoral injection or in vitro cytotoxicity (Yoon et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…High transfection efficiency and a high survival rate have been reported in both NK cell lines and primary NK cells. Much higher transfection efficiency was achieved using mRNA compared to using DNA [148][149][150][151][152]. Introduction by nucleofection has also been tried, but the efficiency was not high [153,154].…”
Section: Genetic Modification-gene Transfer To Nk Cellsmentioning
confidence: 99%
“…Where activating receptors did not sufficiently elicit an antitumor response, researchers augmented the antitumor effect of NK cells by expression of chimeric Ag receptors. [9][10][11] Ultimately, the success of NK cell adoptive immunotherapy for cancer depends not only on target recognition but also on homing of NK cells to the tumor target in vivo. Thus, the effector cells must express the appropriate chemokine receptors.…”
Section: Introductionmentioning
confidence: 99%
“…Although investigators have used viral vectors to gene modify NK cell lines 10,24 and primary NK cells, 9,25 because of safety concerns over integrating viral vectors there has been a recent shift in emphasis toward nonviral methods of gene transfer, particularly nonintegrating, mRNA-based electroporation approaches. 11 However, electroporation of NK cells has been difficult in that the transfection efficiency and viability of NK cells are low, and high-throughput electroporation methods for gene modifying clinically relevant NK cell numbers are currently lacking.…”
Section: Introductionmentioning
confidence: 99%