ArticleJournal for immunotherapy of cancer2024
IL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.Cell reports. Medicine · 2026Article
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- Biochemical signals from the extracellular matrix in inflammation and tumour immunology.Nature reviews. Immunology · 2026Review
- Cancer-associated fibroblasts -derived Tenascin-C activates the Hippo/TAZ pathway to suppress ferroptosis and confer cisplatin resistance in esophageal cancer.Scientific reports · 2026Article
- CAR-T cell therapy for pediatric solid tumors: armored CAR-T cells and beyond.Cancer metastasis reviews · 2026Review
- Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
- Antigen Specificity and Cell Engineering Determine CAR T Cell Efficacy in Group 3 Medulloblastoma.Research square · 2026Article
- Targeting Macrophages in Immunotherapy: The Ascent of CAR-Macrophages.International journal of molecular sciences · 2026Review
- Oncofetal antigens as emerging targets in chimeric antigen receptor (CAR)-T cell-based immunotherapies: opportunities and challenges.Frontiers in cell and developmental biology · 2026Review
- Diversity within ovarian cancer subtypes and their tumor microenvironment.Frontiers in oncology · 2026Review
- TNC-targeted CAR-macrophage therapy alleviates liver fibrosis in mice.Military Medical Research · 2025Article
- Targeting the extracellular matrix with Tenascin-C-specific CAR T cells extends survival in preclinical models of glioblastoma.Journal for immunotherapy of cancer · 2025Article
- Dual targeting of solid tumors using cytokine-induced killer cells modified with a CAR anti-tenascin C and a secretable EGFRxCD3 bispecific antibody.Cancer immunology, immunotherapy : CII · 2025Article
- Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer.NPJ precision oncology · 2025Article
- Targeting Regnase-1 unleashes CAR T cell antitumor activity for osteosarcoma and creates a proinflammatory tumor microenvironment.bioRxiv : the preprint server for biology · 2025Article
- Mapping Knowledge Structure and Themes Trends of Ewing Sarcoma: A Text-Mining Study.Annals of surgical oncology · 2025Article
- Tumor-Associated Extracellular Matrix Obstacles for CAR-T Cell Therapy: Approaches to Overcoming.Current oncology (Toronto, Ont.) · 2025Review
- CAR T cell therapy for central nervous system solid tumors: current progress and future directions.Frontiers in immunology · 2025Review
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Authors and funding
18 authors.
Funding
Abstract
backgroundOncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).
methodsTo determine the expression of the oncofetal version of tenascin C (TNC) encoding the C domain (C.TNC) in pediatric brain and solid tumors, we used quantitative reverse transcription PCR and immunohistochemistry. Genetically modified T cells were generated from human peripheral blood mononuclear cells and evaluated in vitro and in vivo.
resultsWe demonstrate that C.TNC is expressed on a protein level in pediatric tumors, including diffuse intrinsic pontine glioma, osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. We generate C.TNC-CAR T cells and establish that these recognize and kill C.TNC-positive tumor cells. However, their antitumor activity in vivo is limited. To improve the effector function of C.TNC-CAR T cells, we design a leucine zipper-based chimeric cytokine receptor that activates interleukin-18 signaling pathways (Zip18R). Expression of Zip18R in C.TNC-CAR T cells improves their ability to secrete cytokines and expand in repeat stimulation assays. C.TNC-CAR.Zip18R T cells also have significantly greater antitumor activity in vivo compared with unmodified C.TNC-CAR T cells.
conclusionsOur study identifies the C domain of the ECM protein TNC as a promising CAR T-cell therapy for pediatric solid tumors and brain tumors. While we focus here on pediatric cancer, our work has relevance to a broad range of adult cancers that express C.TNC.
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