ArticleCancers2020
The Influence of Chimeric Antigen Receptor Structural Domains on Clinical Outcomes and Associated Toxicities.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- A new hope with CAR T-cell therapy for refractory idiopathic inflammatory myopathies: a systematic review.Journal of translational medicine · 2026Pooled it
- CAR signaling instructs divergent metabolic reprogramming and functional fates in αβ and γδ T cells.Cellular & molecular immunology · 2026Article
- Cellular therapies in systemic lupus erythematosus: recent progress and future directions.Clinical rheumatology · 2026Review
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Emerging immunotherapeutic strategies for malignant serous effusions: current evidence and future directions.Frontiers in oncology · 2026Review
- Application and prospects of genetic engineering in CAR-NK cell therapy.Frontiers in immunology · 2025Review
- Comparison of seven CD19 CAR designs in engineering NK cells for enhancing anti-tumour activity.Cell proliferation · 2024Article
- Review
- Complexities in comparing the impact of costimulatory domains on approved CD19 CAR functionality.Journal of translational medicine · 2023Review
- Next Generation CD44v6-Specific CAR-NK Cells Effective against Triple Negative Breast Cancer.International journal of molecular sciences · 2023Article
- Mutated Flt3Lg Provides Reduced Flt3 Recycling Compared to Wild-Type Flt3Lg and Retains the Specificity of Flt3Lg-Based CAR T-Cell Targeting in AML Models.International journal of molecular sciences · 2023Article
- Insights into Cancer Immunotherapies: Recent Breakthroughs, Opportunities, and Challenges.Cancers · 2023Article
- T cell and B cell antigen receptors share a conserved core transmembrane structure.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma.Haematologica · 2022Article
- Article
- Linkers: An Assurance for Controlled Delivery of Antibody-Drug Conjugate.Pharmaceutics · 2022Review
- CD19-Targeted Immunotherapies for Diffuse Large B-Cell Lymphoma.Frontiers in immunology · 2022Review
- NK Cells Armed with Chimeric Antigen Receptors (CAR): Roadblocks to Successful Development.Cells · 2021Review
- Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.Journal of experimental & clinical cancer research : CR · 2021Review
- In Vivo Cell Tracking Using PET: Opportunities and Challenges for Clinical Translation in Oncology.Cancers · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B cell malignancies, improving patient survival and long-term remission. Nonetheless, over 50% of patients experience severe treatment-related toxicities including cytokine release syndrome (CRS) and neurotoxicity. Differences in severity of toxic side-effects among anti-CD19 CARs suggest that the choice of costimulatory domain makes a significant contribution to toxicity, but comparisons are complicated by additional differences in the hinge and transmembrane (TM) domains of the most commonly used CARs in the clinic, segments that have long been considered to perform purely structural roles. In this perspective, we examine clinical and preclinical data for anti-CD19 CARs with identical antigen-binding (FMC63) and signalling (CD3ζ) domains to unravel the contributions of different hinge-TM and costimulatory domains. Analysis of clinical trials highlights an association of the CD28 hinge-TM with higher incidence of CRS and neurotoxicity than the corresponding sequences from CD8, regardless of whether the CD28 or the 4-1BB costimulatory domain is used. The few preclinical studies that have systematically varied these domains similarly support a strong and independent role for the CD28 hinge-TM sequence in high cytokine production. These observations highlight the value that a comprehensive and systematic interrogation of each of these structural domains could provide toward developing fundamental principles for rational design of safer CAR-T cell therapies.
Indexed as
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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.