ArticleStem cell research & therapy2021
Targeted integration of EpCAM-specific CAR in human induced pluripotent stem cells and their differentiation into NK cells.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 25 citations in OpenAlex.
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Pluripotent stem cell-derived chimeric antigen receptor-natural killer cells targeting epidermal growth factor receptor 2 for cancer immunotherapy.BMB reports · 2025Article
- Natural killer cell membrane manipulation for augmented immune synapse and anticancer efficacy.Materials today. Bio · 2025Review
- IPSC‑derived NK cells for immunotherapy and therapeutic perspective (Review).Molecular medicine reports · 2025Review
- Engineering and targeting potential of CAR NK cells in colorectal cancer.Chinese medical journal · 2025Review
- Chimeric antigen receptor NK-92 cell function is modulated by HLA class I expression of target cells.iScience · 2025Article
- Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- Allogeneic chimeric antigen receptor T cells for children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.Haematologica · 2024Review
- Genetic Manipulation Approaches to Enhance the Clinical Application of NK Cell-Based Immunotherapy.Stem cells translational medicine · 2024Review
- Manufacturing CAR-NK against tumors: Who is the ideal supplier?Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Recent Advancements in Biomaterials for Chimeric Antigen Receptor T Cell Immunotherapy.Biomaterials research · 2024Review
- Joining Forces: The Combined Application of Therapeutic Viruses and Nanomaterials in Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Advances in NK cell therapy for brain tumors.NPJ precision oncology · 2023Review
- Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors.Cancer communications (London, England) · 2023Review
- CD44v6 specific CAR-NK cells for targeted immunotherapy of head and neck squamous cell carcinoma.Frontiers in immunology · 2023Article
- Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.Cells, tissues, organs · 2023Review
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRedirection of natural killer (NK) cells with chimeric antigen receptors (CAR) is attractive in developing off-the-shelf CAR therapeutics for cancer treatment. However, the site-specific integration of a CAR gene into NK cells remains challenging.
methodsIn the present study, we genetically modified human induced pluripotent stem cells (iPSCs) with a zinc finger nuclease (ZFN) technology to introduce a cDNA encoding an anti-EpCAM CAR into the adeno-associated virus integration site 1, a "safe harbour" for transgene insertion into human genome, and next differentiated the modified iPSCs into CAR-expressing iNK cells.
resultsWe detected the targeted integration in 4 out of 5 selected iPSC clones, 3 of which were biallelically modified. Southern blotting analysis revealed no random integration events. iNK cells were successfully derived from the modified iPSCs with a 47-day protocol, which were morphologically similar to peripheral blood NK cells, displayed NK phenotype (CD56+CD3-), and expressed NK receptors. The CAR expression of the iPSC-derived NK cells was confirmed with RT-PCR and flow cytometry analysis. In vitro cytotoxicity assay further confirmed their lytic activity against NK cell-resistant, EpCAM-positive cancer cells, but not to EpCAM-positive normal cells, demonstrating the retained tolerability of the CAR-iNK cells towards normal cells.
conclusionLooking ahead, the modified iPSCs generated in the current study hold a great potential as a practically unlimited source to generate anti-EpCAM CAR iNK cells.
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