ArticleInternational journal of molecular sciences2021
CRISPR-Cas9-Mediated TIM3 Knockout in Human Natural Killer Cells Enhances Growth Inhibitory Effects on Human Glioma Cells.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
- CRISPR-Based Gene Therapy for Brain Disease.Molecular neurobiology · 2026Review
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- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- The Role of NK Cells in Cancer Immunotherapy: Mechanisms, Evasion Strategies, and Therapeutic Advances.Biomedicines · 2025Review
- The Role of TIM-3 in Glioblastoma Progression.Cells · 2025Review
- CRISPR targeting of mmu-miR-21a through a single adeno-associated virus vector prolongs survival of glioblastoma-bearing mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Unraveling the immunosuppressive microenvironment of glioblastoma and advancements in treatment.Frontiers in immunology · 2025Review
- Research Progress of NK Cells in Glioblastoma Treatment.OncoTargets and therapy · 2025Review
- Overcoming immune evasion with innovative multi-target approaches for glioblastoma.Frontiers in immunology · 2025Review
- Unraveling Glioblastoma: TME Implication and Gene Therapy Advances.Current gene therapy · 2025Review
- Mesothelin expression correlates with elevated inhibitory immune activity in patients with colorectal cancer.Cancer gene therapy · 2024Article
- Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.Pharmaceutics · 2024Review
- Characterization of HIF-1α Knockout Primary Human Natural Killer Cells Including Populations in Allogeneic Glioblastoma.International journal of molecular sciences · 2024Article
- Bulk RNA sequencing reveals the comprehensive genetic characteristics of human cord blood-derived natural killer cells.Regenerative therapy · 2024Article
- Mesothelin expression correlates with elevated inhibitory immune activity in patients with colorectal cancer.Research square · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Natural Killer (NK) cells are potent cytotoxic effector cells against tumor cells inducing GBM cells; therefore, NK cell based- immunotherapy might be a promising target in GBM. T cell immunoglobulin mucin family member 3 (TIM3), a receptor expressed on NK cells, has been suggested as a marker of dysfunctional NK cells. We established TIM3 knockout in NK cells, using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9). Electroporating of TIM3 exon 2- or exon 5-targeting guide RNA- Cas9 protein complexes (RNPs) inhibited TIM3 expression on NK cells with varying efficacy. T7 endonuclease I mutation detection assays showed that both RNPs disrupted the intended genome sites. The expression of other checkpoint receptors, i.e., programmed cell death 1 (PD1), Lymphocyte-activation gene 3 (LAG3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and TACTILE (CD96) were unchanged on the TIM3 knockout NK cells. Real time cell growth assays revealed that TIM3 knockout enhanced NK cell-mediated growth inhibition of GBM cells. These results demonstrated that TIM3 knockout enhanced human NK cell mediated cytotoxicity on GBM cells. Future, CRISPR-Cas9 mediated TIM3 knockout in NK cells may prove to be a promising immunotherapeutic alternative in patient with GBM.
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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.