ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Dissecting the Mechanisms Underlying the Cytokine Release Syndrome (CRS) Mediated by T-Cell Bispecific Antibodies.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Association of Ferritin Levels With Cytokine Release Syndrome in CAR T-Cell Therapy: A Systematic Review and Meta-Analysis.Cancer medicine · 2026Pooled it
- Efficacy and safety of bispecific antibodies versus other antitumor therapies in solid tumors: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Trial
- A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings.Frontiers in immunology · 2024Trial
- Article
- CD20 bispecific T-cell engager depletes B-cell progenitors preventing EBV-associated lymphomagenesis in humanized mice.Blood advances · 2026Article
- Endothelial Injury as a Potential Contributor to Cardiovascular Toxicity in Hematologic Malignancies.Diseases (Basel, Switzerland) · 2026Review
- Research Progress and Optimization Strategies of Bispecific Antibody Therapies for CLDN18.2-Positive Gastric Cancer.Journal of gastrointestinal cancer · 2026Review
- Narrative review of research progress and future development of bispecific antibodies in lung cancer: opportunities and challenges.Translational lung cancer research · 2026Review
- Fc-engineering for improved cancer immunotherapy.Biochemical Society transactions · 2026Review
- Nanobody-based targeted cancer therapy and immunotherapy: fear not the future.Acta pharmacologica Sinica · 2026Review
- Successful Tarlatamab Rechallenge After Recurrent High-Grade Cytokine Release Syndrome in Chromothripsis-Mediated SCLC: A Case Report.JTO clinical and research reports · 2026Article
- Safety and Efficacy of Mosunetuzumab: Experience in the Hospital Cardinale Giovanni Panico.Antibodies (Basel, Switzerland) · 2026Article
- First-in-human phase 1 study of RO7119929, an oral TLR7 agonist prodrug, in patients with advanced primary or metastatic liver cancers.Journal for immunotherapy of cancer · 2026Article
- Article
- Rats exposed to a low resource environment in early life display sex differences in blood pressure, autonomic activity, and brain and kidney pro-inflammatory markers during adulthood.Biology of sex differences · 2026Article
- Biomarkers of activity from a phase I study of cergutuzumab amunaleukin in patients with advanced solid tumors.Journal for immunotherapy of cancer · 2026Article
- Immune cell engagers in lung cancer.Frontiers in immunology · 2026Review
- Mechanism of Bispecific Antibodies and Clinical Research Advances in Lung Cancer.Current cancer drug targets · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
Corrections and comments
- Commented on by
Authors and funding
23 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTarget-dependent TCB activity can result in the strong and systemic release of cytokines that may develop into cytokine release syndrome (CRS), highlighting the need to understand and prevent this complex clinical syndrome. EXPERIMENTAL
designWe explored the cellular and molecular players involved in TCB-mediated cytokine release by single-cell RNA-sequencing of whole blood treated with CD20-TCB together with bulk RNA-sequencing of endothelial cells exposed to TCB-induced cytokine release. We used the in vitro whole blood assay and an in vivo DLBCL model in immunocompetent humanized mice to assess the effects of dexamethasone, anti-TNFα, anti-IL6R, anti-IL1R, and inflammasome inhibition, on TCB-mediated cytokine release and antitumor activity.
resultsActivated T cells release TNFα, IFNγ, IL2, IL8, and MIP-1β, which rapidly activate monocytes, neutrophils, DCs, and NKs along with surrounding T cells to amplify the cascade further, leading to TNFα, IL8, IL6, IL1β, MCP-1, MIP-1α, MIP-1β, and IP-10 release. Endothelial cells contribute to IL6 and IL1β release and at the same time release several chemokines (MCP-1, IP-10, MIP-1α, and MIP-1β). Dexamethasone and TNFα blockade efficiently reduced CD20-TCB-mediated cytokine release whereas IL6R blockade, inflammasome inhibition, and IL1R blockade induced a less pronounced effect. Dexamethasone, IL6R blockade, IL1R blockade, and the inflammasome inhibitor did not interfere with CD20-TCB activity, in contrast to TNFα blockade, which partially inhibited antitumor activity.
conclusionsOur work sheds new light on the cellular and molecular players involved in cytokine release driven by TCBs and provides a rationale for the prevention of CRS in patients treated with TCBs. See related commentary by Luri-Rey et al., p. 4320.
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.