ArticleNature medicine2018
Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 889 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Advanced Immune Gene and Cell Therapies for Liver Metastases
Pilot Study of Pre-emptive Anakinra for the Prevention of Severe Cytokine Release Syndrome in Children and Young Adults With B-Acute Lymphoblastic Leukemia Receiving Chimeric Antigen Receptor (CAR) T Cells
Who cites it
889 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,344 citations in OpenAlex.
- The safety and efficacy of chimeric antigen receptor-T cell therapy in solid malignancies: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Point-of-care fresh CAR T cells for pediatric or young adult BCP-ALL that is relapsed/refractory or in very-high-risk first relapse.Blood advances · 2025Trial
- Single-cell dynamics of breakthrough toxicities after anakinra prophylaxis for axicabtagene ciloleucel in lymphoma.Blood advances · 2025Trial
- Review
- Bench-to-Bedside Perspectives on the Development of Soluble TCR-Based Protein Biologics: Current Landscape, Control Strategy and Future Direction.International journal of molecular sciences · 2026Review
- Clonal Hematopoiesis and CAR T Cell Therapy: From Biological Crosstalk to Clinical Implications.International journal of laboratory hematology · 2026Review
- Drug-controlled CAR T cells through the regulation of cell-cell interactions.Nature chemical biology · 2026Article
- Scalable generation of hematopoietic stem cell-engineered off-the-shelf mono-specific cytotoxic T cells targeting solid tumors.Cell reports. Medicine · 2026Article
- Stepwise Evolution of Immunodeficient Mouse Models: Focus on NCG Strains and Their Applications in Humanized Immune System Research.Vaccines · 2026Review
- CRS and ICANS: Early detection and personalized management.Blood research · 2026Review
- Characterization of CAR-T cell factors that contribute to myeloid cell activation.Gene therapy · 2026Article
- Cardiotoxicity of T cell immunotherapies.Nature reviews. Cardiology · 2026Review
- Anakinra Prophylaxis for Recurrent Severe ICANS Associated With Tarlatamab in Small Cell Lung Cancer: Case Report.JTO clinical and research reports · 2026Article
- The evolving role of cytokines for CAR-T cell manufacturing and beyond.Nature biomedical engineering · 2026Review
- IFN-γ-driven iNOS induction in macrophages mediates CAR T cell resistance in B cell lymphoma.Nature communications · 2026Article
- Neural regulation of cancer: from microenvironmental hijacking to systemic circuit co-option.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Multifaceted roles of CD44 in cancer progression and targeted therapeutic strategies.Experimental & molecular medicine · 2026Review
- Article
- Coordinated expansion of CD163bioRxiv : the preprint server for biology · 2026Article
- Chimeric antigen receptor T cell therapy cardiotoxicity: a narrative review.Cardio-oncology (London, England) · 2026Review
829 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the clinic, chimeric antigen receptor-modified T (CAR T) cell therapy is frequently associated with life-threatening cytokine-release syndrome (CRS) and neurotoxicity. Understanding the nature of these pathologies and developing treatments for them are hampered by the lack of appropriate animal models. Herein, we describe a mouse model recapitulating key features of CRS and neurotoxicity. In humanized mice with high leukemia burden, CAR T cell-mediated clearance of cancer triggered high fever and elevated IL-6 levels, which are hallmarks of CRS. Human monocytes were the major source of IL-1 and IL-6 during CRS. Accordingly, the syndrome was prevented by monocyte depletion or by blocking IL-6 receptor with tocilizumab. Nonetheless, tocilizumab failed to protect mice from delayed lethal neurotoxicity, characterized by meningeal inflammation. Instead, the IL-1 receptor antagonist anakinra abolished both CRS and neurotoxicity, resulting in substantially extended leukemia-free survival. These findings offer a therapeutic strategy to tackle neurotoxicity and open new avenues to safer CAR T cell therapies.
Indexed as
Identifiers
What OpenQuestion holds
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.