ArticleNeuro-oncology2019
Targeting hypoxia downstream signaling protein, CAIX, for CAR T-cell therapy against glioblastoma.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 68 citations in OpenAlex.
- Expression patterns of carbonic anhydrase IX and immune response biomarkers in pediatric gliomas and glioneuronal tumors.Journal of neuro-oncology · 2026Article
- A transcriptome-defined TAM-rich phenotype identifies a macrophage-enriched, hypoxia-linked immune contexture in glioblastoma: multi-cohort transcriptomic validation and local histopathological correlation.Frontiers in immunology · 2026Article
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Challenges and limitations of chimeric antigen receptor T-cell therapies in solid tumors: why are approvals restricted to hematologic malignancies?Journal of hematology & oncology · 2025Review
- Advancements and challenges in CAR-T cell therapy for solid tumors: A comprehensive review of antigen targets, strategies, and future directions.Cancer cell international · 2025Review
- Spatiotemporal dynamics of tumor-CAR T-cell interaction following local administration in solid cancers.PLoS computational biology · 2025Article
- Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma.Biomarker research · 2025Review
- Systematic Analysis of CA9 as a Pan-Cancer Marker for Prognosis and Immunity.Cancer informatics · 2025Article
- New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma.Frontiers in immunology · 2025Review
- CAR-armored-cell therapy in solid tumor treatment.Journal of translational medicine · 2024Review
- Challenges and strategies in relation to effective CAR-T cell immunotherapy for solid tumors.Medical oncology (Northwood, London, England) · 2024Review
- Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects.Molecular cancer · 2024Article
- Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches.Frontiers in pharmacology · 2024Review
- Optimizing CAR-T Therapy for Glioblastoma.Molecular diagnosis & therapy · 2023Review
- Review
- Gene Targets of CAR-T Cell Therapy for Glioblastoma.Cancers · 2023Review
- Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma.Journal of clinical medicine · 2023Review
- Runx3-overexpression cooperates with ex vivo AKT inhibition to generate receptor-engineered T cells with better persistence, tumor-residency, and antitumor ability.Journal for immunotherapy of cancer · 2023Article
- CAR T cells: engineered immune cells to treat brain cancers and beyond.Molecular cancer · 2023Review
- Current and potential roles of immuno-PET/-SPECT in CAR T-cell therapy.Frontiers in medicine · 2023Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundGlioblastoma survival remains unchanged despite continuing therapeutic innovation. Herein, we aim to (i) develop chimeric antigen receptor (CAR) T cells with a specificity to a unique antigen, carbonic anhydrase IX (CAIX), which is expressed in the hypoxic microenvironment characteristic of glioblastoma, and (ii) demonstrate its efficacy with limited off-target effects.
methodsFirst we demonstrated expression of CAIX in patient-derived glioblastoma samples and available databases. CAR T cells were generated against CAIX and efficacy was assessed in 4 glioblastoma cell lines and 2 glioblastoma stem cell lines. Cytotoxicity of anti-CAIX CAR T cells was assessed via interferon gamma, tumor necrosis factor alpha, and interleukin-2 levels when co-cultured with tumor cells. Finally, we assessed efficacy of direct intratumoral injection of the anti-CAIX CAR T cells on an in vivo xenograft mouse model using the U251 luciferase cell line. Tumor infiltrating lymphocyte analyses were performed.
resultsWe confirm that CAIX is highly expressed in glioblastoma from patients. We demonstrate that CAIX is a suitable target for CAR T-cell therapy using anti-CAIX CAR T cells against glioblastoma in vitro and in vivo. In our mouse model, a 20% cure rate was observed without detectable systemic effects.
conclusionsBy establishing the specificity of CAIX under hypoxic conditions in glioblastoma and highlighting its efficacy as a target for CAR T-cell therapy, our data suggest that anti-CAIX CAR T may be a promising strategy to treat glioblastoma. Direct intratumoral injection increases anti-CAIX CAR T-cell potency while limiting its off-target effects.
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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.