ArticleCytotherapy2014
T cells redirected to interleukin-13Rα2 with interleukin-13 mutein--chimeric antigen receptors have anti-glioma activity but also recognize interleukin-13Rα1.
Article in Cytotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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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.
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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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The efficacy of chimeric antigen receptor (CAR) immunotherapy in animal models for solid tumors: A systematic review and meta-analysis.PloS one · 2017Pooled it
- Review
- Immunotheranostics in Solid Tumors: Longitudinal Tracking of Human IL13Rα2 CAR-T Cells In Vivo.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- CAR-T cell therapy in glioblastoma: from αβ to γδ T-cell platforms.Oncology reviews · 2026Review
- Computational structural optimization enhances IL13Rα2 - B7-H3 tandem CAR T cells to overcome antigen-heterogeneity-mediated tumor escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- IL-13/IL-13Rα2 axis promotes proliferation of angiosarcoma cells.Scientific reports · 2025Article
- Review
- Breaking barriers: exploring blood-brain barrier crossing mechanisms with nanomedicine for effective glioma treatment.3 Biotech · 2025Review
- IL13Rα2-Targeting Antibodies for Immuno-PET in Solid Malignancies.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Pooled screening for CAR function identifies novel IL-13Rα2-targeted CARs for treatment of glioblastoma.Journal for immunotherapy of cancer · 2025Article
- Expression features of targets for anti-glioma CAR-T cell immunotherapy.Journal of neuro-oncology · 2025Article
- Combining immunotherapy with radiotherapy for glioblastoma: recent advances and challenges.Frontiers in oncology · 2025Review
- Identification and characterisation of novel CAR-T cells to target IL13Rα2 positive human glioma in vitro and in vivo.Clinical and translational medicine · 2024Article
- CAR-T Cell Therapy: From the Shop to Cancer Therapy.International journal of molecular sciences · 2023Review
- Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy.International journal of molecular sciences · 2023Review
- Engineering CAR-T cells for radiohapten capture in imaging and radioimmunotherapy applications.Theranostics · 2023Article
- Inclusion of 4-1BB Costimulation Enhances Selectivity and Functionality of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells.Cancer research communications · 2023Article
- Clinical and Translational Advances in Glioma Immunotherapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- A Conceptual Framework for Inducing T Cell-Mediated Immunity Against Glioblastoma.Seminars in immunopathology · 2022Review
- Engineered IL13 variants direct specificity of IL13Rα2-targeted CAR T cell therapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND
aimsOutcomes for patients with glioblastoma remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL) 13Rα2, human epidermal growth factor receptor 2, epidermal growth factor variant III or erythropoietin-producing hepatocellular carcinoma A2 has shown promise for the treatment of glioma in preclinical models. On the basis of IL13Rα2 immunotoxins that contain IL13 molecules with one or two amino acid substitutions (IL13 muteins) to confer specificity to IL13Rα2, investigators have constructed CARS with IL13 muteins as antigen-binding domains. Whereas the specificity of IL13 muteins in the context of immunotoxins is well characterized, limited information is available for CAR T cells.
methodsWe constructed four second-generation CARs with IL13 muteins with one or two amino acid substitutions, and evaluated the effector function of IL13-mutein CAR T cells in vitro and in vivo.
resultsT cells expressing all four CARs recognized IL13Rα1 or IL13Rα2 recombinant protein in contrast to control protein (IL4R) as judged by interferon-γ production. IL13 protein produced significantly more IL2, indicating that IL13 mutein-CAR T cells have a higher affinity to IL13Rα2 than to IL13Rα1. In cytotoxicity assays, CAR T cells killed IL13Rα1- and/or IL13Rα2-positive cells in contrast to IL13Rα1- and IL13Rα2-negative controls. Although we observed no significant differences between IL13 mutein-CAR T cells in vitro, only T cells expressing IL13 mutein-CARs with an E13K amino acid substitution had anti-tumor activity in vivo that resulted in a survival advantage of treated animals.
conclusionsOur study highlights that the specificity/avidity of ligands is context-dependent and that evaluating CAR T cells in preclinical animal model is critical to assess their potential benefit.
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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.