ArticleNature communications2024
Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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
39 citing papers in PubMed, 41 citations in OpenAlex.
- Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma.Journal for immunotherapy of cancer · 2025Trial
- Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial.Journal of hematology & oncology · 2024Trial
- From technological iteration to clinical breakthrough: advances of CAR-T cell therapy in autoimmune diseases.Annals of medicine · 2026Review
- Munc13-4-STX7 inhibitors impair endosomal TLR activation and systemic inflammation.Nature chemical biology · 2026Article
- Coordinated expansion of CD163bioRxiv : the preprint server for biology · 2026Article
- Mapping clinical CAR-T cells: insights from scRNA-seq.Trends in molecular medicine · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Chimeric antigen receptor T-cell therapies related to immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome: Diagnosis, high-risk factors, and management.Chinese medical journal · 2026Review
- Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma.Blood neoplasia · 2026Article
- Th17-driven CD8Cell death & disease · 2026Article
- Are we there yet? The road to faster and more efficient CAR T cell manufacturing.Journal of biological engineering · 2026Review
- Physiological, patho-physiological, and potential therapeutic roles for neutrophils in cancer & beyond.Frontiers in immunology · 2026Review
- Affinity and costimulatory architecture-associated toxicity in mesothelin-targeted TCR-mimetic CAR-T cells.Frontiers in immunology · 2026Article
- A 3D engineered multiple myeloma niche for evaluating CAR T cell therapy.Frontiers in bioengineering and biotechnology · 2026Article
- Antibody-Drug Conjugates, T-Cell Engager Bispecific Antibodies and Chimeric Antigen Receptor T Cells for Multiple Myeloma: What's the Current Status?Targeted oncology · 2026Review
- Metabolic biomarkers for predicting onset and severity of CAR-T therapy-induced cytokine release syndrome in multiple myeloma.Frontiers of medicine · 2025Article
- 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
- Cytokine release syndrome complicated with sepsis induced by tislelizumab in a patient with advanced hepatocellular carcinoma: A case report.Human vaccines & immunotherapeutics · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytokine release syndrome (CRS) is the most common complication of chimeric antigen receptor redirected T cells (CAR-T) therapy. CAR-T toxicity management has been greatly improved, but CRS remains a prime safety concern. Here we follow serum cytokine levels and circulating immune cell transcriptomes longitudinally in 26 relapsed/refractory multiple myeloma patients receiving the CAR-T product, ciltacabtagene autoleucel, to understand the immunological kinetics of CRS. We find that although T lymphocytes and monocytes/macrophages are the major overall cytokine source in manifest CRS, neutrophil activation peaks earlier, before the onset of severe symptoms. Intracellularly, signaling activation dominated by JAK/STAT pathway occurred prior to cytokine cascade and displayed regular kinetic changes. CRS severity is accurately described and potentially predicted by temporal cytokine secretion signatures. Notably, CAR-T re-expansion is found in three patients, including a fatal case characterized by somatic TET2-mutation, clonal expanded cytotoxic CAR-T, broadened cytokine profiles and irreversible hepatic toxicity. Together, our findings show that a latent phase with distinct immunological changes precedes manifest CRS, providing an optimal window and potential targets for CRS therapeutic intervention and that CAR-T re-expansion warrants close clinical attention and laboratory investigation to mitigate the lethal risk.
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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.