ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Engineering the TGFβ Receptor to Enhance the Therapeutic Potential of Natural Killer Cells as an Immunotherapy for Neuroblastoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 81 citations in OpenAlex.
- Circumventing Ewing sarcoma tumor microenvironment resistance by IL1RAP CAR-modified TGFβ1-imprinted natural killer cells in combination with IL-15 agonist and anti-GD2 antibody.Journal for immunotherapy of cancer · 2026Article
- Review
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CD39Science translational medicine · 2026Article
- One-step knock-in CAR constructs in human NK cells enable scalable, TGFβ1-resistant immunotherapy for solid tumors.Theranostics · 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
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- 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
- Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.Journal of experimental & clinical cancer research : CR · 2025Review
- Advancing CAR-based cell therapies for solid tumours: challenges, therapeutic strategies, and perspectives.Molecular cancer · 2025Review
- Natural killer cell-based immunotherapy for cancer.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma.European journal of cancer (Oxford, England : 1990) · 2025Article
- Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy.Annals of laboratory medicine · 2025Review
- Article
- Mitochondrial priming in therapy-induced senescence: implications for CAR-T/NK immunosenolytic therapy.Frontiers in immunology · 2025Review
- Perspective: IL-15 cytokine-armored NK cells as ready-to-use immunotherapy for diverse malignancies: therapeutic potential and toxicity risks.Frontiers in immunology · 2025Review
- Enhancing the physiological characteristics of chimeric antigen receptor natural killer cells by synthetic biology.Frontiers in immunology · 2025Review
- Natural killer cells in neuroblastoma: immunological insights and therapeutic perspectives.Cancer metastasis reviews · 2024Review
- Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells.Cell stem cell · 2024Article
- Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges.Cancers · 2024Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe ability of natural killer (NK) cells to lyse allogeneic targets, without the need for explicit matching or priming, makes them an attractive platform for cell-based immunotherapy. Umbilical cord blood is a practical source for generating banks of such third-party NK cells for "off-the-shelf" cell therapy applications. NK cells are highly cytolytic, and their potent antitumor effects can be rapidly triggered by a lack of HLA expression on interacting target cells, as is the case for a majority of solid tumors, including neuroblastoma. Neuroblastoma is a leading cause of pediatric cancer-related deaths and an ideal candidate for NK-cell therapy. However, the antitumor efficacy of NK cells is limited by immunosuppressive cytokines in the tumor microenvironment, such as TGFβ, which impair NK cell function and survival. EXPERIMENTAL
designTo overcome this, we genetically modified NK cells to express variant TGFβ receptors, which couple a mutant TGFβ dominant-negative receptor to NK-specific activating domains. We hypothesized that with these engineered receptors, inhibitory TGFβ signals are effectively converted to activating signals.
resultsModified NK cells exhibited higher cytotoxic activity against neuroblastoma in a TGFβ-rich environment
conclusionsOur results support the development of "off-the-shelf" gene-modified NK cells, that overcome TGFβ-mediated immune evasion, in patients with neuroblastoma and other TGFβ-secreting malignancies.
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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.