ArticleCancer immunology research2023
Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function.
Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Metabolic reprogramming via LDHB confers resistance to lactate-induced dysfunction and enhanced antitumor activity in hiPSC-Derived NK cells.Stem cell reports · 2026Article
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- CAR-NK cell therapy for hematological malignancies.Blood advances · 2026Review
- Article
- Innate immune cells in chimeric antigen receptor therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- CAR NK cell production from human cord blood NK progenitor cells is enhanced by stimulation of the IL-15 receptor.Cancer immunology, immunotherapy : CII · 2025Article
- Review
- SCO-ph: Microfluidic Dynamic Phenotyping Platform for High-Throughput Screening of Single Cell Acidification.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Review
- Secretome and Cellular Composition of Peripheral Blood Mononuclear Cells Cultured in the Presence of Cell Feeder or Interleukins.Bulletin of experimental biology and medicine · 2025Article
- Integrated ATAC-seq and RNA-seq analysis identifies key regulatory elements in NK cells activated with feeder cells and IL-2.Bioengineering & translational medicine · 2025Article
- Interleukin-21 engineering enhances CD19-specific CAR-NK cell activity against B-cell lymphoma via enriched metabolic pathways.Experimental hematology & oncology · 2025Article
- Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy.Immune network · 2025Review
- A ligand-centered framework for γδ T cell activation in colorectal cancer revealed by single-cell and transformer-based perturbation.Frontiers in immunology · 2025Article
- NK cell-based immunotherapy strategies for myeloid leukemia.Frontiers in immunology · 2025Review
- A Critical Role of Culture Medium Selection in Maximizing the Purity and Expansion of Natural Killer Cells.Cells · 2024Article
- Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.Nature communications · 2024Article
- Chimeric antigen receptor-natural killer cell therapy: current advancements and strategies to overcome challenges.Frontiers in immunology · 2024Review
- Dynamics of natural killer cell function upon recurrent stimulation.Biotechnology progressArticle
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells are frequently expanded for the clinic using irradiated, engineered K562 feeder cells expressing a core transgene set of membrane-bound (mb) IL15 and/or mbIL21 together with 41BBL. Prior comparisons of mbIL15 to mbIL21 for NK expansion lack comparisons of key attributes of the resulting NK cells, including their high-dimensional phenotype, polyfunctionality, the breadth and potency of cytotoxicity, cellular metabolism, and activity in xenograft tumor models. Moreover, despite multiple rounds of K562 stimulation, studies of sequential use of mbIL15- and mbIL21-based feeder cells are absent. We addressed these gaps and found that using mbIL15- versus mbIL21-based feeder cells drove distinct phenotypic and functional profiles. Feeder cells expressing mbIL15 alone drove superior functionality by nearly all measures, whereas those expressing mbIL21 alone drove superior yield. In combination, most attributes resembled those imparted by mbIL21, whereas in sequence, NK yield approximated that imparted by the first cytokine, and the phenotype, transcriptome, and function resembled that driven by the second cytokine, highlighting the plasticity of NK cell differentiation. The sequence mbIL21 followed by mbIL15 was advantageous in achieving significant yields of highly functional NK cells that demonstrated equivalent in vivo activity to those expanded by mbIL15 alone in two of three xenograft models. Our findings define the impact of mbIL15 versus mbIL21 during NK expansion and reveal a previously underappreciated tradeoff between NK yield and function for which sequential use of mbIL21-based followed by mbIL15-based feeder cells may be the optimal approach in many settings.
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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.