ArticleThe Journal of clinical investigation2023
IL-18-secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06348797 (Phase I Clinical Study on Safety and Feasibility of DLL3 Targeted α-PD-L1/4-1BB Modifying Chimeric Antigen Receptor T-cells in Patients With Relapsed or Refractory Small Cell Lung Cancer), which is not on this map. Cited by 133 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Phase I Clinical Study on Safety and Feasibility of DLL3 Targeted α-PD-L1/4-1BB Modifying Chimeric Antigen Receptor T-cells in Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)
Who cites it
133 citing papers in PubMed, 156 citations in OpenAlex.
- Boosting CAR T cell efficacy in cancer with metabolic insights from design to diet.Nature reviews. Cancer · 2026Review
- Recent advancements and persisting challenges in the evolution of next generation car t cell therapy for solid malignancies: a comprehensive review.Immunologic research · 2026Review
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- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- Single-Cell and Spatial Transcriptomics Reframe the Immunosuppressive Microenvironment of Neuroendocrine Neoplasms.Cancers · 2026Review
- IL-18 derived from microwave-ablated osteosarcoma facilitates antitumor response.Journal for immunotherapy of cancer · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- Progress in the development of cytokine armoured CAR T cells.Nature reviews. Immunology · 2026Review
- Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells.Cell death & disease · 2026Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Targeted cellular micropharmacies deliver therapeutic agents to the brain.EMBO molecular medicine · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Immunological consequences of chemotherapy: implications for cancer immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Article
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- CAR immune cell therapy strategies and advances for lung cancer.Discover oncology · 2026Review
- Engineering CAR-Vδ2 T cells to boost persistence and anti-tumor function.bioRxiv : the preprint server for biology · 2026Article
- IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Patients with small cell lung cancer (SCLC) generally have a poor prognosis and a median overall survival of only about 13 months, indicating the urgent need for novel therapies. Delta-like protein 3 (DLL3) has been identified as a tumor-specific cell surface marker on neuroendocrine cancers, including SCLC. In this study, we developed a chimeric antigen receptor (CAR) against DLL3 that displays antitumor efficacy in xenograft and murine SCLC models. CAR T cell expression of the proinflammatory cytokine IL-18 greatly enhanced the potency of DLL3-targeting CAR T cell therapy. In a murine metastatic SCLC model, IL-18 production increased the activation of both CAR T cells and endogenous tumor-infiltrating lymphocytes. We also observed an increased infiltration, repolarization, and activation of antigen-presenting cells. Additionally, human IL-18-secreting anti-DLL3 CAR T cells showed an increased memory phenotype, less exhaustion, and induced durable responses in multiple SCLC models, an effect that could be further enhanced with anti-PD-1 blockade. All together, these results define DLL3-targeting CAR T cells that produce IL-18 as a potentially promising novel strategy against DLL3-expressing solid tumors.
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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.