ArticleCells2020
Hinge and Transmembrane Domains of Chimeric Antigen Receptor Regulate Receptor Expression and Signaling Threshold.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.
- Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.Frontiers in immunology · 2022Pooled it
- CAR signaling instructs divergent metabolic reprogramming and functional fates in αβ and γδ T cells.Cellular & molecular immunology · 2026Article
- Cardiotoxicity of T cell immunotherapies.Nature reviews. Cardiology · 2026Review
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- High-Precision Intrinsic Interactome Elucidation of Chimeric Antigen Receptors via Photocatalytic Micromapping (μMap-CAR).Journal of the American Chemical Society · 2026Article
- A Scalable Lentiviral Workflow for Laboratory-Scale Generation of BCMA/GPRC5D Co-Transduced CAR-T Cells in Multiple Myeloma.Current issues in molecular biology · 2026Article
- Humanized biparatopic nanobody-based CAR-T cells overcome antigen-heterogeneity in multiple myeloma.Journal of translational medicine · 2026Article
- Structure-Function Insights into Immune Receptors Drive Innovation in CAR-T Cell Therapy.Current issues in molecular biology · 2026Review
- LRRC15-CAR T Cells for the Treatment of Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- NOT-gated chimeric antigen receptor circuits in T and NK cells.Cell systems · 2026Article
- CAR-T cell therapy in breast cancer management: expanding horizon and overcoming challenges beyond hematologic cancers.Molecular biology reports · 2026Review
- Enhanced antitumoral activity of the academic CAR-T ARI0002h against normal and low BCMA-expressing myeloma cells after incorporating a transmembrane CD28 domain.Journal for immunotherapy of cancer · 2026Article
- CAR-macrophages: a new chapter in cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Article
- CAR T-Cell Immunotherapy in Neuroautoimmune Diseases: Focus on the Central Nervous System.Biomedicines · 2026Review
- Advances in CAR-T Cell Therapy: From Structural Design Innovations to Clinical Translation Challenges.Journal of Cancer · 2026Review
- Advanced strategies to enhance the safety, persistence, and efficacy of CAR-T cells in solid tumors.Frontiers in immunology · 2026Review
- CAR T-cells for the treatment of CNS malignancies.Frontiers in immunology · 2026Review
- A new era in CAR-NK cell therapy: from technological innovations to clinical applications.World journal of pediatrics : WJP · 2026Review
- Overcoming Resistance and Relapse in CAR-T and CAR-NK Cell Therapies: From Bench to Bedside.Research (Washington, D.C.) · 2026Article
- Advancing breast cancer treatment through dual targeting CAR T cell therapy.Discover oncology · 2025Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR)-T cells have demonstrated significant clinical potential; however, their strong antitumor activity may cause severe adverse effects. To ensure efficacy and safe CAR-T cell therapy, it is important to understand CAR's structure-activity relationship. To clarify the role of hinge and transmembrane domains in CAR and CAR-T cell function, we generated different chimeras and analyzed their expression levels and antigen-specific activity on CAR-T cells. First, we created a basic CAR with hinge, transmembrane, and signal transduction domains derived from CD3ζ, then we generated six CAR variants whose hinge or hinge/transmembrane domains originated from CD4, CD8α, and CD28. CAR expression level and stability on the T cell were greatly affected by transmembrane rather than hinge domain. Antigen-specific functions of most CAR-T cells depended on their CAR expression levels. However, CARs with a CD8α- or CD28-derived hinge domain showed significant differences in CAR-T cell function, despite their equal expression levels. These results suggest that CAR signaling intensity into T cells was affected not only by CAR expression level, but also by the hinge domain. Our discoveries indicate that the hinge domain regulates the CAR signaling threshold and the transmembrane domain regulates the amount of CAR signaling via control of CAR expression level.
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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.