ArticleScientific reports2019
Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 124 citations in OpenAlex.
- A systematic review of the last two decades of NK cell-based clinical trials: state of the art of AML therapy.BMC cancer · 2025Pooled it
- Donor NKG2A/NKG2C Immunophenotype Influences the GMP-Compliant Manufacturing Potential of NK Cells for Adoptive Immunotherapy.Cancers · 2026Article
- Cytokine-induced expandable memory NK cells with significant metabolic, epigenetic remodeling, and persistence properties.Cell death discovery · 2026Article
- Cultivating Functional Natural Killer Cells from Mobilized Hematopoietic Stem Cells in Heavily Pretreated Hematologic Malignancies.International journal of molecular sciences · 2026Article
- Improved expansion of peripheral blood and iPSC-derived natural killer cells for clinical applications.Cell reports methods · 2026Article
- Article
- Developing a multimodal therapy for glioblastoma using oncolytic virus delivering CD19 and EGFRvIII antigens and bi-specific CARs.Nature communications · 2026Article
- Non-viral TcBuster transposon engineering of CD70-CAR natural killer cells for the treatment of osteosarcoma.Molecular therapy. Oncology · 2026Article
- Article
- Optimization of Natural Killer Cell Expansion with K562-mbIL-18/-21 Feeder Cells and Assurance of Feeder Cell-free Products.Annals of laboratory medicine · 2026Article
- Current Developments of CAR-T and CAR-NK Cell Therapies for Ovarian Cancer.Stem cell reviews and reports · 2026Review
- HOPX is required for the generation of umbilical cord blood-derived memory-like NK cells induced by three cytokines.Frontiers in immunology · 2026Article
- Metabolic licensing and restriction of innate immunity in the tumor microenvironment.Frontiers in immunology · 2026Review
- Fibrinogen depletion prevents non-dissociable cell aggregates of feeder-derived NK cell products.Frontiers in immunology · 2026Article
- The Activity of EGFR CAR NK and CAR T Cells against EGFR Inhibitor-Resistant NSCLC and Drug-Tolerant Persister Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- Review
- A Scalable Protocol for Ex Vivo Production of CAR-Engineered Human NK Cells.Methods and protocols · 2025Article
- A novel feeder cell based on 4-1BBL and membrane-bound IL-21/IL-15 induce highly expansion and anti-tumor effect of natural killer cells.BMC biotechnology · 2025Article
- In Vitro Expansion and Transduction of Primary NK Cells Using Feeder Cells Expressing Costimulatory Molecules and IL-21.Cancer science · 2025Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
NK cell adoptive therapy is a promising cancer therapeutic approach, but there are significant challenges that limiting its feasibility and clinical efficacy. One difficulty is the paucity of clinical grade manufacturing platforms to support the large scale expansion of highly active NK cells. We created an NK cell feeder cell line termed 'NKF' through overexpressing membrane bound IL-21 that is capable of inducing robust and sustained proliferation (>10,000-fold expansion at 5 weeks) of highly cytotoxic NK cells. The expanded NK cells exhibit increased cytotoxic function against a panel of blood cancer and solid tumor cells as compared to IL-2-activated non-expanded NK cells. The NKF-expanded NK cells also demonstrate efficacy in mouse models of human sarcoma and T cell leukemia. Mechanistic studies revealed that membrane-bound IL-21 leads to an activation of a STAT3/c-Myc pathway and increased NK cell metabolism with a shift towards aerobic glycolysis. The NKF feeder cell line is a promising new platform that enables the large scale proliferation of highly active NK cells in support of large scale third party NK cell clinical studies that have been recently intiatied. These results also provide mechanistic insights into how membrane-bound IL-21 regulates NK cell expansion.
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Registered trials
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.