ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2023
An Interleukin-15 Superagonist Enables Antitumor Efficacy of Natural Killer Cells Against All Molecular Variants of SCLC.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- From biology to the clinic: research evidence and therapeutic advances of TROP2-targeted antibody-drug conjugates in small cell lung cancer.Translational lung cancer research · 2026Review
- Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.Cancer cell · 2026Article
- Rewiring tumor cytokine networks to enhance immune checkpoint blockade: mechanisms, engineering, and clinical translation.Journal of experimental & clinical cancer research : CR · 2026Review
- The ATR inhibitor tuvusertib (M1774) sensitizes prostate carcinoma to natural killer cell-mediated cytotoxicity, which is further augmented by the IL-15 receptor superagonist N-803.Cancer immunology, immunotherapy : CII · 2025Article
- Reprogramming natural killer cells in the tumor microenvironment: Challenges and therapeutic opportunities.Cytokine & growth factor reviews · 2025Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Molecular cancer therapeutics · 2025Review
- Combination Therapy Approaches to Enhance the Efficacy of ERV-Targeting Vaccines in Cancer.Cancer immunology research · 2025Review
- Combination therapy with expanded natural killer cells and atezolizumab exerts potent antitumor immunity in small cell lung cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Stimulation of cGAS-STING pathway as a challenge in the treatment of small cell lung cancer: a feasible strategy?British journal of cancer · 2024Review
- Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches.Immunity, inflammation and disease · 2024Review
- Xianling Lianxia formula improves the efficacy of trastuzumab by enhancing NK cell-mediated ADCC in HER2-positive BC.Journal of pharmaceutical analysis · 2024Article
- Peripheral NK cells identified as the predictor of response in extensive-stage small cell lung cancer patients treated with first-line immunotherapy plus chemotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Beyond PD(L)-1 Blockade in Microsatellite-Instable Cancers: Current Landscape of Immune Co-Inhibitory Receptor Targeting.Cancers · 2024Review
- Review
- Fulvestrant increases the susceptibility of enzalutamide-resistant prostate cancer cells to NK-mediated lysis.Journal for immunotherapy of cancer · 2023Article
- In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice.Molecules (Basel, Switzerland) · 2023Article
- Exploiting an Interleukin-15 Heterodimeric Agonist (N803) for Effective Immunotherapy of Solid Malignancies.Cells · 2023Review
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
introductionSCLC is a highly aggressive tumor with a 5-year survival rate of less than 6%. A heterogeneous disease, SCLC is classified into four subtypes that include tumors with neuroendocrine and non-neuroendocrine features. Immune checkpoint blockade has been recently added for the frontline treatment of SCLC; however, this therapy has only led to modest clinical improvements. The lack of clinical benefit in a cancer type known to have a high tumor mutational burden has been attributed to poor T-cell infiltration and low expression of MHC-class I in most SCLC tumors. In an attempt to devise a more effective immunotherapeutic regimen, this study investigated an alternate approach on the basis of the use of the clinical-stage interleukin-15 superagonist, N-803.
methodsPreclinical models of SCLC spanning all molecular subtypes were used to evaluate the susceptibility of SCLC to natural killer (NK)-mediated lysis in vitro, including NK cells activated by N-803. Antitumor activity of N-803 was evaluated in vivo with a xenograft model of SCLC.
resultsIn vitro and in vivo data revealed differences in susceptibility of SCLC subtypes to lysis by NK cells and that NK cells activated by N-803 effectively lyse SCLC tumor cells across all variant subtypes, regardless of their expression of MHC-class I.
conclusionsThese findings highlight the potential of a novel immune-based intervention using a cytokine-based therapeutic option for the treatment of SCLC. We hypothesize that N-803 may provide benefit to most patients with SCLC, including those with immunologically cold tumors lacking MHC expression.
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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.