ArticleFrontiers in immunology2019
High Cytotoxic Efficiency of Lentivirally and Alpharetrovirally Engineered CD19-Specific Chimeric Antigen Receptor Natural Killer Cells Against Acute Lymphoblastic Leukemia.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 108 citations in OpenAlex.
- CAR-NK cell therapy for hematological malignancies.Blood advances · 2026Review
- Efficient NK cell transduction with VSV-G-pseudotyped lentiviral vectors.Molecular therapy. Advances · 2026Article
- A Feeder Cell-Free System for Chimeric Antigen Receptor Gene Transduction Into Natural Killer Cells.Bio-protocol · 2026Article
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Baboon endogenous retrovirus (ERV) envelope pseudotyped lentiviral vectors outperform human ERV lentivectors for transduction of T, B, NK and HSPCs.Gene therapy · 2026Article
- Review
- High-titer human packaging cells producing γ-retroviral vectors pseudotyped with engineered baboon endogenous retrovirus (BaEV) envelope proteins.Frontiers in molecular medicine · 2026Article
- Natural killer cells in adoptive cell therapy: current landscape of genetic engineering strategies.Oncoimmunology · 2025Review
- Natural killer cell membrane manipulation for augmented immune synapse and anticancer efficacy.Materials today. Bio · 2025Review
- Precision targeting of rhabdomyosarcoma by combining primary CAR NK cells and radiotherapy.Journal for immunotherapy of cancer · 2025Article
- Optimizing viral transduction in immune cell therapy manufacturing: key process design considerations.Journal of translational medicine · 2025Review
- Migration Dynamics of Human NK Cell Preparations in Microchannels and Their Invasion Into Patient-Derived Tissue.Journal of cellular and molecular medicine · 2025Article
- Immunotherapy of chimeric antigen receptor NK cells: status and its promising future.Frontiers in immunology · 2025Review
- Recent advances in tumor immunotherapy based on NK cells.Frontiers in immunology · 2025Review
- CAR-NK cells: harnessing the power of natural killers for advanced cancer therapy.Frontiers in immunology · 2025Review
- Construction of stable packaging cell lines for large-scale industrial BaEV-enveloped retroviral vector production.Frontiers in immunology · 2025Article
- CAR-NK cell therapy: promise and challenges in solid tumors.Frontiers in immunology · 2025Review
- CRISPR/Cas9 editing of NKG2A improves the efficacy of primary CD33-directed chimeric antigen receptor natural killer cells.Nature communications · 2024Article
- T cell receptor-directed antibody-drug conjugates for the treatment of T cell-derived cancers.Molecular therapy. Oncology · 2024Article
- Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.Pharmaceutics · 2024Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autologous chimeric antigen receptor-modified (CAR) T cells with specificity for CD19 showed potent antitumor efficacy in clinical trials against relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL). Contrary to T cells, natural killer (NK) cells kill their targets in a non-antigen-specific manner and do not carry the risk of inducing graft vs. host disease (GvHD), allowing application of donor-derived cells in an allogenic setting. Hence, unlike autologous CAR-T cells, therapeutic CD19-CAR-NK cells can be generated as an off-the-shelf product from healthy donors. Nevertheless, genetic engineering of peripheral blood (PB) derived NK cells remains challenging and optimized protocols are needed. In our study, we aimed to optimize the generation of CD19-CAR-NK cells by retroviral transduction to improve the high antileukemic capacity of NK cells. We compared two different retroviral vector platforms, the lentiviral and alpharetroviral, both in combination with two different transduction enhancers (Retronectin and Vectofusin-1). We further explored different NK cell isolation techniques (NK cell enrichment and CD3/CD19 depletion) to identify the most efficacious methods for genetic engineering of NK cells. Our results demonstrated that transduction of NK cells with RD114-TR pseudotyped retroviral vectors, in combination with Vectofusin-1 was the most efficient method to generate CD19-CAR-NK cells. Retronectin was potent in enhancing lentiviral/VSV-G gene delivery to NK cells but not alpharetroviral/RD114-TR. Furthermore, the Vectofusin-based transduction of NK cells with CD19-CARs delivered by alpharetroviral/RD114-TR and lentiviral/RD114-TR vectors outperformed lentiviral/VSV-G vectors. The final generated CD19-CAR-NK cells displayed superior cytotoxic activity against CD19-expressing target cells when compared to non-transduced NK cells achieving up to 90% specific killing activity. In summary, our findings present the use of RD114-TR pseudotyped retroviral particles in combination with Vectofusin-1 as a successful strategy to genetically modify PB-derived NK cells to achieve highly cytotoxic CD19-CAR-NK cells at high yield.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.