ArticleJournal of translational medicine2022
Optimizing NK-92 serial killers: gamma irradiation, CD95/Fas-ligation, and NK or LAK attack limit cytotoxic efficacy.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Efficacy of chimeric antigen receptor natural killer cells in treatment of ovarian cancer. A meta-analysis of pre-clinical studies.Immunologic research · 2026Pooled it
- 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
- CD45 as a multifunctional target in immune regulation and therapeutic delivery.Journal of translational medicine · 2026Review
- Characterization of a Cytokine-Independent STAT5 Activator.Biomedicines · 2026Article
- Transcriptional Profile Change of NK-92 Cells in Presence of Cytokines, TGFβ Signaling Pathway Inhibitor and CDK7/12/13 Kinase Inhibitor.International journal of molecular sciences · 2026Article
- State of the Art of CAR-NK Cell Therapy in Multiple Myeloma: A Comprehensive Review of Cell Sources and Target Antigens.International journal of molecular sciences · 2025Review
- Review
- Natural killer cell-based immunotherapy for cancer.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Chimeric antigen receptor therapies: Development, design, and implementation.The Journal of allergy and clinical immunology · 2025Review
- The clinical landscape of CAR NK cells.Experimental hematology & oncology · 2025Review
- Curative timed NK cell-based immunochemotherapy aborts brain tumour recurrence driven by mesenchymal glioma stem cells.Acta neuropathologica communications · 2025Article
- Single-chain variable fragment affinity tuning can optimize anti-AML CAR-NK cell functionality.Journal for immunotherapy of cancer · 2025Article
- Antitumor effects of natural killer cells derived from gene-engineered human-induced pluripotent stem cells on hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2025Article
- Adoptive NK cell therapy in AML: progress and challenges.Clinical and experimental medicine · 2025Review
- 2B4 co-stimulation and dasatinib modulation enhance anti-CD19 CAR-NK-92 cell cytotoxicity.Frontiers in immunology · 2025Article
- Repurposing anti-mesothelin CAR-NK immunotherapy against colorectal cancer.Journal of translational medicine · 2024Article
- Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.Journal of nanobiotechnology · 2024Review
- Apoptotic Receptors and CD107a Expression by NK Cells in an Interaction Model with Trophoblast Cells.Current issues in molecular biology · 2024Article
- Dynamic Transcriptional Programs During Single NK Cell Killing: Connecting Form to Function in Cellular Immunotherapy.Cellular and molecular bioengineering · 2024Article
- Antitumor activity of genetically engineered NK-cells in non-hematological solid tumor: a comprehensive review.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe NK cell line NK-92 and its genetically modified variants are receiving attention as immunotherapies to treat a range of malignancies. However, since NK-92 cells are themselves tumors, they require irradiation prior to transfer and are potentially susceptible to attack by patients' immune systems. Here, we investigated NK-92 cell-mediated serial killing for the effects of gamma-irradiation and ligation of the death receptor Fas (CD95), and NK-92 cell susceptibility to attack by activated primary blood NK cells.
methodsTo evaluate serial killing, we used
resultsNK-92 cells were able to kill up to 14 Raji cells per NK-92 cell in 8 h. NK-92 cells retained high cytotoxic activity immediately after irradiation with 10 Gy but the cells surviving irradiation lost > 50% activity 1 day after irradiation. Despite high expression of CD95, NK-92 cells maintained their viability following overnight Fas/CD95-ligation but lost some cytotoxic activity. However, 1 day after irradiation, NK-92 cells were more susceptible to Fas ligation, resulting in decreased cytotoxic activity of the cells surviving irradiation. Irradiated NK-92 cells were also susceptible to killing by both unstimulated and IL-2 activated primary NK cells (LAK). In contrast, non-irradiated NK-92 cells were more resistant to attack by NK and LAK cells.
conclusionsIrradiation is deleterious to both the survival and cytotoxicity mediated by NK-92 cells and renders the NK-92 cells susceptible to Fas-initiated death and death initiated by primary blood NK cells. Therefore, replacement of irradiation as an antiproliferative pretreatment and genetic deletion of Fas and/or NK activation ligands from adoptively transferred cell lines are indicated as new approaches to increase therapeutic efficacy.
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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.