ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Comprehensive Serum Proteome Profiling of Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome Patients with B-Cell ALL Receiving CAR T19.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
51 citing papers in PubMed, 3 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Axicabtagene Ciloleucel versus Tisagenlecleucel for Relapsed or Refractory Large B Cell Lymphoma: A Systematic Review and Meta-Analysis.Transplantation and cellular therapy · 2024Pooled it
- The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).Annals of the rheumatic diseases · 2023Pooled it
- The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).Arthritis & rheumatology (Hoboken, N.J.) · 2023Pooled it
- Case study of CD19 CAR T therapy in a subject with immune-mediate necrotizing myopathy treated in the RESET-Myositis phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Trial
- Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.Cell reports. Medicine · 2026Article
- Differential cytokine architecture in patients treated with CART19 versus CART22.Journal for immunotherapy of cancer · 2026Article
- Arterial Catheter-Associated Proximal Ischemic Injury in Critically Ill Children: Evidence of Endothelial Dysfunction and Immune Dysregulation.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2026Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Review
- Nanoparticles-enhanced CAR-T cell therapy: current advances and future directions.Biomarker research · 2026Review
- Review
- Managing Treatment-Emergent Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome Following CAR-T Cell Therapy: A Case-Based Review of the use of Emapalumab.Hematological oncology · 2026Review
- How can we balance risk and benefit of interleukin-18 armored T cell therapies?Experimental biology and medicine (Maywood, N.J.) · 2026Review
- CAR-T manufacturing reduces heterogeneity between CIDP and multiple myeloma patient-derived T cells.Theranostics · 2026Article
- Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas.Frontiers in immunology · 2026Review
- Predictive markers for the efficacy of CAR T-cell therapy: the interplay between CAR T-cell fitness and systemic immunity.Blood advances · 2025Review
- Digital Biomarkers of Cytokine Release Syndrome: Scoping Review and Ontology Development of the Role and Relevance of Digital Measures Using a Mixed Methods Approach.Journal of medical Internet research · 2025Article
- Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.Molecular cancer · 2025Review
- Identifying Immune Response Protein Biomarkers in Parkinson's-Related Cognitive Impairment and Depression.Molecular neurobiology · 2025Article
- A Method for Comparing Proteins Measured in Serum and Plasma by Olink Proximity Extension Assay.Molecular & cellular proteomics : MCP · 2025Article
Corrections and comments
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Authors and funding
26 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo study the biology and identify markers of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in children after chimeric antigen receptor T-cell (CAR T) treatment. EXPERIMENTAL
designWe used comprehensive proteomic profiling to measure over 1,400 serum proteins at multiple serial timepoints in a cohort of patients with B-cell acute lymphoblastic leukemia treated with the CD19-targeted CAR T CTL019 on two clinical trials.
resultsWe identified fms-like tyrosine kinase 3 (FLT3) and mast cell immunoglobulin-like receptor 1 (MILR1) as preinfusion predictive biomarkers of severe CRS. We demonstrated that CRS is an IFNγ-driven process with a protein signature overlapping with hemophagocytic lymphohistiocytosis (HLH). We identified IL18 as a potentially targetable cytokine associated with the development of ICANS.
conclusionsWe identified preinfusion biomarkers that can be used to predict severe CRS with a sensitivity, specificity, and accuracy superior to the current gold standard of disease burden. We demonstrated the fundamental role of the IFNγ pathway in driving CRS, suggesting CRS and carHLH are overlapping rather than distinct phenomena, an observation with important treatment implications. We identified IL18 as a possible targetable cytokine in ICANS, providing rationale for IL18 blocking therapies to be translated into clinical trials in ICANS.
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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.