ArticleFrontiers in immunology2021
Therapeutic Potential of TNFα and IL1β Blockade for CRS/ICANS in CAR-T Therapy
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 3 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Pooled it
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- A Systematic Review on the Dual Role of Interleukin-1 in CAR T-Cell Therapy: Enhancer and Mitigator.Iranian biomedical journal · 2024Pooled it
- Characterization of CAR-T cell factors that contribute to myeloid cell activation.Gene therapy · 2026Article
- Mechanobiology of CAR-T cell therapy: regulatory mechanisms and strategies for enhanced antitumor immunity.Journal of translational medicine · 2026Review
- Cardiotoxicity induced by multiple myeloma therapies: mechanistic convergence across proteasome inhibitors, CAR-T, and bispecific antibodies.Blood cancer journal · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Endotheliopathy in CAR T-Cell Therapy: Mechanistic Insights into the VWF/ADAMTS13 Axis and the Angiopoietin-Tie2 Pathway.TH open : companion journal to thrombosis and haemostasis · 2026Review
- Selinexor Reduces the Immunosuppression of Macrophages and Synergizes With CD19 CAR-T Cells Against B-Cell Lymphoma.Cancer science · 2025Article
- Review
- CAR-T cell therapy for glioblastoma: advances, challenges, and future directions.Annals of medicine and surgery (2012) · 2025Review
- A Proteomics Outlook on the Molecular Effectors of CAR-T Cell Therapy in Cancer Management.Journal of proteome research · 2025Review
- Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies.Annals of hematology · 2025Review
- The Struggle Between Chimeric Antigen Receptor T-Cell Therapy and Neurological Complications in Acute Lymphoblastic Leukemia Treatment.Current issues in molecular biology · 2025Review
- Bidirectional Communication Between the Innate and Adaptive Immune Systems.Annual review of immunology · 2025Review
- Targeting P-selectin and interleukin-1β in mice with sickle cell disease: effects on vaso-occlusion, liver injury and organ iron deposition.Haematologica · 2025Article
- CART-induced eosinophilic colitis with good response to corticosteroids and infliximab: a case report.Therapeutic advances in medical oncology · 2025Article
- Endothelial dysfunction and hemostatic imbalance in CAR T-cell-associated toxicities: pathophysiological insights and the role of circulating biomarkers.Frontiers in immunology · 2025Review
- Multicellular Cancer-Stroma Spheres (CSS) for In Vitro Assessment of CAR-T Cell-Associated Toxicity.Cells · 2024Article
- Nanotechnology in Advancing Chimeric Antigen Receptor T Cell Therapy for Cancer Treatment.Pharmaceutics · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) strongly hampered the broad clinical applicability of chimeric antigen receptor T cell (CAR-T) therapy. Vascular endothelial activation has been suggested to contribute to the development of CRS and ICANS after CAR-T therapy. However, therapeutic strategies targeting endothelial dysfunction during CAR-T therapy have not been well studied yet. Here, we found that tumor necrosis factor α (TNFα) produced by CAR-T cells upon tumor recognition and interleukin 1β (IL1β) secreted by activated myeloid cells were the main cytokines in inducing endothelial activation. Therefore, we investigated the potential effectiveness of TNFα and IL1β signaling blockade on endothelial activation in CAR-T therapy. The blockade of TNFα and IL1β with adalimumab and anti-IL1β antibody respectively, as well as the application of focal adhesion kinase (FAK) inhibitor, effectively ameliorated endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Moreover, adalimumab and anti-IL1β antibody exerted synergistic effect on the prevention of endothelial activation induced by CAR-T, tumor cells, and myeloid cells. Our results indicate that TNFα and IL1β blockade might have therapeutic potential for the treatment of CAR-T therapy-associated CRS and neurotoxicity.
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