Details

Autor(en) / Beteiligte

• Bexte, Tobias
• Botezatu, Lacramioara
• Miskey, Csaba
• Gierschek, Fenja
• Moter, Alina
• Wendel, Philipp
• Reindl, Lisa Marie
• Campe, Julia
• Villena-Ossa, Jose Francisco
• Gebel, Veronika
• Stein, Katja
• Cathomen, Toni
• Cremer, Anjali
• Wels, Winfried S.
• Hudecek, Michael
• Ivics, Zoltán
• Ullrich, Evelyn

Titel

Engineering of potent CAR NK cells using non-viral Sleeping Beauty transposition from minimalistic DNA vectors

Ist Teil von

• Molecular therapy, 2024-07, Vol.32 (7), p.2357-2372

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] Ullrich and colleagues present an innovative non-viral SB transposon/transposase-based system for CAR-NK cell engineering. The SB-transposon system is an efficient, safe, and cost-effective approach to virus-free engineering of highly functional CAR-NK cells, which can be suitable for cancer immunotherapy of leukemia. as well as many other malignancies.