AI Article Synopsis
- NK cells are powerful immune cells with proven effectiveness in cancer therapy, especially when enhanced by CAR technology, allowing them to target cancer cells more specifically.
- The study introduces a novel non-viral method using the Sleeping Beauty transposon system and minicircles to engineer CAR NK cells, resulting in stable CAR expression and improved genetic integration compared to traditional methods.
- These engineered CAR NK cells showed greater effectiveness against leukemia cells in lab models, suggesting a promising avenue for developing cost-effective and safe cancer immunotherapies.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287004 | PMC |
| http://dx.doi.org/10.1016/j.ymthe.2024.05.022 | DOI Listing |
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