ArticleCytotherapy2021
Transient blockade of TBK1/IKKε allows efficient transduction of primary human natural killer cells with vesicular stomatitis virus G-pseudotyped lentiviral vectors.
Article in Cytotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Efficient NK cell transduction with VSV-G-pseudotyped lentiviral vectors.Molecular therapy. Advances · 2026Article
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Modulating viscosity improves lentiviral transduction of NK cells: A simple solution to a persistent problem.Molecular therapy. Advances · 2026Article
- Engineered CAR-NK Cells for Cancer Immunotherapy: Lentiviral-Based CAR Transduction of NK-92 Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Natural killer cell-based cancer immunotherapy: from basics to clinical trials.Experimental hematology & oncology · 2024Review
- Methodological Approaches for Increasing the Retroviral Transduction Efficiency of Primary NK Cells.Current pharmaceutical design · 2024Article
- A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?Frontiers in immunology · 2024Review
- Chimeric antigen receptor-natural killer cell therapy: current advancements and strategies to overcome challenges.Frontiers in immunology · 2024Review
- CAR-NK cell therapy for glioblastoma: what to do next?Frontiers in oncology · 2023Review
- Gene-Based Natural Killer Cell Therapies for the Treatment of Pediatric Hematologic Malignancies.Hematology/oncology clinics of North America · 2022Review
- Taking Lessons from CAR-T Cells and Going Beyond: Tailoring Design and Signaling for CAR-NK Cells in Cancer Therapy.Frontiers in immunology · 2022Review
- Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity.Science translational medicine · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND
aimsVesicular stomatitis virus G (VSV-G)-pseudotyped lentiviral vectors (LVs) are widely used to reliably generate genetically modified, clinical-grade T-cell products. However, the results of genetically modifying natural killer (NK) cells with VSV-G LVs have been variable. The authors explored whether inhibition of the IKK-related protein kinases TBK1 and IKKε, key signaling molecules of the endosomal TLR4 pathway, which is activated by VSV-G, would enable the reliable transduction of NK cells by VSV-G LVs.
methodsThe authors activated NK cells from peripheral blood mononuclear cells using standard procedures and transduced them with VSV-G LVs encoding a marker gene (yellow fluorescent protein [YFP]) or functional genes (chimeric antigen receptors [CARs], co-stimulatory molecules) in the presence of three TBK1/IKKε inhibitors (MRT67307, BX-795, amlexanox). NK cell transduction was evaluated by flow cytometry and/or western blot and the functionality of expressed CARs was evaluated in vitro.
resultsBlocking TBK1/IKKε during transduction of NK cells enabled their efficient transduction by VSV-G LVs as judged by YFPexpression of 40-50%, with half maximal effective concentrations of 1.1 µM (MRT67307), 5 µM (BX-795) and 24.8 µM (amlexanox). Focusing on MRT67307, the authors successfully generated NK cells expressing CD19-CARs or HER2-CARs with an inducible co-stimulatory molecule. CAR NK cells exhibited increased cytolytic activity and ability to produce cytokines in comparison to untreated controls, confirming CAR functionality.
conclusionsThe authors demonstrate that inhibition of TBK1/IKKε enables the reliable generation of genetically modified NK cells using VSV-G LVs. The authors' protocol can be readily adapted to generate clinical-grade NK cells and thus has the potential to facilitate the clinical evaluation of genetically modified NK cell-based therapeutics in the future.
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