ArticleNeuro-oncology2024
Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated blood-brain barrier opening: A novel combinatorial immunotherapy regimen for gliomas.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05864534 (A Phase 2a Trial of Immune Modulation in Combination With Ultrasound-mediated Blood Brain Barrier Opening in Patients With Newly Diagnosed Glioblastoma), which is not on this map. Cited by 31 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.
The trial behind it
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.
A Phase 2a Trial of Immune Modulation in Combination With Ultrasound-mediated Blood Brain Barrier Opening in Patients With Newly Diagnosed Glioblastoma
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Focused ultrasound-induced blood-brain barrier modulation for drug delivery in recurrent glioblastoma: A systematic review.The Indian journal of medical research · 2026Pooled it
- Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.Molecular cancer · 2026Review
- Anti-PD-1 single-chain variable fragments in cancer immunotherapy: from molecular engineering to clinical translation.Cancer chemotherapy and pharmacology · 2026Review
- Glioma-intrinsic MAPK/ERK signaling promotes immunotherapy efficacy through T cell infiltration and interferon responses.Nature communications · 2026Article
- Development of skull-implanted ultrasound for blood-brain barrier opening and drug delivery in neuro-oncology.Neuro-oncology advances · 2026Review
- Tumor-Derived Exosomes Deliver Membrane-Bound Fgl2 to Activate FcγRIIB-Mediated Immunosuppression in Myeloid-Derived Suppressor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Applications of transcranial focused ultrasound for primary brain tumors.Neuro-oncology advances · 2026Review
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- Regulatory T Cells in Diabetic Wound Healing: A Comprehensive Review.Journal of inflammation research · 2026Review
- Targeting regulatory T cells in glioblastoma: from mechanistic insights to novel immunotherapeutic strategies.Frontiers in immunology · 2026Review
- Advances in ultrasound-assisted drug delivery and clinical application.Ultrasonics sonochemistry · 2026Review
- Role of elevation of glycolysis in tumor-associated macrophages in glioblastoma immune evasion and therapeutic implications.PNAS nexus · 2026Review
- STING signaling pathway: An oasis in the glioblastoma immune desert.Theranostics · 2026Review
- Immune therapy-related hyperprogressive disease: Molecular mechanisms, biomarkers, and clinical strategies.World journal of clinical oncology · 2025Review
- Recruiting T-cells toward the brain for enhanced glioblastoma chemo-immunotherapy efficacy by co-delivery of cytokines and temozolomide via ultrasound-gated redox-responsive extracellular vesicles.Journal of nanobiotechnology · 2025Article
- CDK12 regulates cellular metabolism to promote glioblastoma growth.JCI insight · 2025Article
- Prospects and applications of NK therapy in the treatment of gliomas (Review).Oncology reports · 2025Review
- Targeting the glioblastoma resection margin with locoregional nanotechnologies.Nature reviews. Clinical oncology · 2025Review
- Ultrasound-responsive nanoparticles for imaging and therapy of brain tumors.Materials today. Bio · 2025Review
- Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
34 authors.
Funding
Abstract
backgroundGlioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers.
methodsWe evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor-associated macrophages/microglia (TAMs).
resultsFcE-aCTLA-4 demonstrated high-affinity binding to FcγRIV, the mouse ortholog of human FcγRIIIA, which was highly expressed in TAMs in human glioblastoma, most robustly at diagnosis. Notably, FcE-aCTLA-4-mediated selective depletion of intratumoral regulatory T cells (Tregs) via TAM-mediated phagocytosis, while sparing peripheral Tregs. Doxorubicin, a chemotherapeutic drug with immunomodulatory functions, was found to upregulate FcγRIIIA on TAMs in glioblastoma patients who received doxorubicin and anti-PD-1 with concomitant LIPU/MB. In murine models of immunotherapy-resistant gliomas, a combinatorial regimen of FcE-aCTLA-4, anti-PD-1, and doxorubicin with LIPU/MB, achieved a 90% cure rate, that was associated robust infiltration of activated CD8+ T cells and establishment of immunological memory as evidenced by rejection upon tumor rechallenge.
conclusionsOur findings demonstrate that FcE-aCTLA-4 promotes robust immunomodulatory and anti-tumor effects in murine gliomas and is significantly enhanced when combined with anti-PD-1, doxorubicin, and LIPU/MB. We are currently investigating this combinatory strategy in a clinical trial (clinicaltrials.gov NCT05864534).
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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.