ArticleJournal for immunotherapy of cancer2023
IL15 modification enables CAR T cells to act as a dual targeting agent against tumor cells and myeloid-derived suppressor cells in GBM.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Chimeric Antigen Receptor-T Cell Therapy for Pediatric and Young Adult Primary Central Nervous System Tumors: A Systematic Review of Early Phase Clinical Trials with a Focus on Diffuse Midline Glioma.Targeted oncology · 2026Pooled it
- In vivo immune cell engineering from bench to clinical reality.Pharmaceutical science advances · 2026Review
- Meditope-Enabled Chimeric Antigen Receptors Facilitate Plug-and-Play Control of T Cells.Cancer immunology research · 2026Article
- Armored Chimeric Antigen Receptor T-cell Therapy Targets Antigen-Heterogeneous Glioma.Cancer research · 2026Article
- Intracranially injected chimeric antigen receptor T cells eradicate glioblastoma cells but have limited potential to persist in the brain in a syngeneic mouse model.Cancer immunology, immunotherapy : CII · 2026Article
- Myeloid-Derived Suppressor Cells: Function, Migration, and Therapeutic Opportunities in Glioblastoma.Cells · 2026Review
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Non-lytic viral immunotherapy induces long-term glioblastoma survival and tumor-specific immunity without eliciting an antiviral response.Nature communications · 2026Article
- Prospects of Chimeric Antigen Receptor T-Cell Therapy in Myelofibrosis: From Immunopathogenesis to Therapeutic Strategies.Cancers · 2026Review
- CAR-engineering of innate and innate-like immune cells: a new horizon in adoptive cell therapy for solid tumors.Journal for immunotherapy of cancer · 2026Review
- Schlafen 5 is an intracellular immune checkpoint and controls IFN responses in pancreatic ductal adenocarcinoma.JCI insight · 2026Article
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions.World journal of clinical oncology · 2026Review
- Obstacles and improvement strategies for CAR-T cell therapy in solid tumors.Discover oncology · 2026Review
- Antibody therapies in glioblastoma: Overcoming micro-environmental barriers.Iranian journal of basic medical sciences · 2026Review
- The dynamic myeloid-enriched microenvironment of glioblastoma: a major challenge to immunotherapy efficacy.Frontiers in immunology · 2026Review
- Immunological Biomarkers in Glioblastoma: Targeting T and NK Cells for Enhanced Diagnosis and Prognosis.Biologics : targets & therapy · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Why CAR T cell therapy fails in renal cell carcinoma.Frontiers in immunology · 2026Review
- Asparaginase enhances CAR-T cell antitumor immunity by asparagine metabolic reprogramming and central memory induction in ALL.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
introductionThe immunosuppressive tumor microenvironment (TME) is a major barrier to the efficacy of chimeric antigen receptor T cells (CAR-T cells) in glioblastoma (GBM). Transgenic expression of IL15 is one attractive strategy to modulate the TME. However, at present, it is unclear if IL15 could be used to directly target myeloid-derived suppressor cells (MDSCs), a major cellular component of the GBM TME. Here, we explored if MDSC express IL15Rα and the feasibility of exploiting its expression as an immunotherapeutic target.
methodsRNA-seq, RT-qPCR, and flow cytometry were used to determine IL15Rα expression in paired peripheral and tumor-infiltrating immune cells of GBM patients and two syngeneic murine GBM models. We generated murine T cells expressing IL13Rα2-CARs and secretory IL15 (CAR.IL15s) or IL13Rα2-CARs in which IL15 was fused to the CAR to serve as an IL15Rα-targeting moiety (CAR.IL15f), and characterized their effector function in vitro and in syngeneic IL13Rα2+glioma models.
resultsIL15Rα was preferentially expressed in myeloid, B, and dendritic cells in patients' and syngeneic GBMs. In vitro, CAR.IL15s and CAR.IL15f T cells depleted MDSC and decreased their secretion of immunosuppressive molecules with CAR.IL15f T cells being more efficacious. Similarly, CAR.IL15f T cells significantly improved the survival of mice in two GBM models. TME analysis showed that treatment with CAR.IL15f T cells resulted in higher frequencies of CD8+T cells, NK, and B cells, but a decrease in CD11b+cells in tumors compared with therapy with CAR T cells.
conclusionsWe demonstrate that MDSC of the glioma TME express IL15Ra and that these cells can be targeted with secretory IL15 or an IL15Rα-targeting moiety incorporated into the CAR. Thus, IL15-modified CAR T cells act as a dual targeting agent against tumor cells and MDSC in GBM, warranting their future evaluation in early-phase clinical studies.
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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.