ArticleNeuro-oncology2022
Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Locoregional and systemic adoptive cellular therapies for pediatric brain tumors: a systematic review of CAR‑T, TCR‑engineered T cells, and NK cell strategies.Neurosurgical review · 2026Pooled it
- FECH, a novel metabolic target influencing CAR T-cell phenotype and function.Biomarker research · 2026Article
- Identification of a novel ion channel-related gene signature to predict prognosis and immune response of gastric cancer.Translational cancer research · 2026Article
- CAR-T cell therapy for pediatric solid tumors: armored CAR-T cells and beyond.Cancer metastasis reviews · 2026Review
- Endogenous and Extracellular Roles of a Tumor Suppressor miR-379-5p in Gastric Cancer.Oncology · 2026Article
- Single-Cell Analysis Links C7+ Cancer-Associated Fibroblasts with Incomplete Resection in Platinum-Sensitive Relapsed Ovarian Cancer.Biomedicines · 2025Article
- Anoikis classification of lung squamous cell carcinoma reveals correlation with clinical prognosis and immune characteristics.Annals of medicine · 2025Article
- Cellular immunotherapies for central nervous system cancers.Neuro-oncology advances · 2025Review
- GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.NPJ precision oncology · 2025Review
- Preliminary exploration of PSMA CAR-T combined with GD2 CAR-T for the treatment of refractory/relapsed gliomas.Journal of translational medicine · 2025Article
- Rational Design and Organoid-Based Evaluation of a Cocktail CAR-γδ T Cell Therapy for Heterogeneous Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Anti-OAcGD2 antibody in combination with ceramide kinase inhibitor mediates potent antitumor cytotoxicity against breast cancer and diffuse intrinsic pontine glioma cells.Molecular and cellular biochemistry · 2025Article
- Therapeutic advantage of combinatorial chimeric antigen receptor T cell and chemotherapies.Pharmacological reviews · 2025Review
- Tumor-derived G-CSF induces an immunosuppressive microenvironment in an osteosarcoma model, reducing response to CAR.GD2 T-cells.Journal of hematology & oncology · 2024Article
- Exploring the potential of the convergence between extracellular vesicles and CAR technology as a novel immunotherapy approach.Journal of extracellular biology · 2024Review
- The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.Neuro-oncology · 2024Article
- CAR T-cell therapy: a potential treatment strategy for pediatric midline gliomas.Acta neurologica Belgica · 2024Review
- GD2-Targeting CAR T-cell Therapy for Patients with GD2+ Medulloblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Pan-cancer analysis of prognostic and immunological role of IL4I1 in human tumors: a bulk omics research and single cell sequencing validation.Discover oncology · 2024Article
- Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening.Journal of experimental & clinical cancer research : CR · 2024Article
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Authors and funding
28 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.
methodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.
resultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.
conclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.
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