ArticleNature immunology2023
Harnessing CD3 diversity to optimize CAR T cells.
Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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
50 citing papers in PubMed, 62 citations in OpenAlex.
- Adoptive cell therapy in lung cancer: progress, challenges, and prospects.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Mechanobiology of CAR-T cell therapy: regulatory mechanisms and strategies for enhanced antitumor immunity.Journal of translational medicine · 2026Review
- A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.Expert reviews in molecular medicine · 2026Review
- Virus-like antigen display delivers a stand-alone danger signal through the BCR that circumvents tolerance.bioRxiv : the preprint server for biology · 2026Article
- Engineering of genetically encoded programmable calcium channel inhibitory binders.Nature communications · 2026Article
- Metabolic engineering of SLC38A2 reprograms glutamine utilization and enhances CAR-macrophage antitumor function in solid tumors.Cancer biology & medicine · 2026Article
- PD-1: CD28 chimeric receptors enhance phenotypic and functional features of T cell subsets.Research in pharmaceutical sciences · 2026Article
- CAR-T cell exhaustion in B cell lymphoma: Current status, mechanisms, and potential solutions.Molecular therapy. Oncology · 2026Review
- Enhancing CAR-T cell activity prediction via fine-tuning protein language models with generated CAR sequences.BMC bioinformatics · 2026Article
- CD147 regulates CD8iScience · 2026Article
- Engineering chimeric antigen receptor CD4 T cells for Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- PTPN6/SHP-1 in autoimmune disease: immune tolerance, regulatory mechanisms, and therapeutic targeting.Frontiers in immunology · 2026Review
- Smart Cells Against Cancer: Advances in Cell-Based Drug Delivery and Diagnostics.Pharmaceutics · 2025Review
- CIMT 2025: Report on the 22Human vaccines & immunotherapeutics · 2025Article
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- CD28 signaling complexes are correlated with patient outcomes in anti-CD19 41BB-costimulation CAR T cell therapy.Journal for immunotherapy of cancer · 2025Article
- Label-free estimation of regulatory T cell activation markers using Raman spectroscopy with machine learning.Scientific reports · 2025Article
- shRNA-based PD-1 suppression preserves memory phenotype and function of CD19-targeted CAR-T cell.Translational cancer research · 2025Article
- CD28-mediated linear and parallel costimulatory signaling cooperatively regulate CAR-T cell functions via CAR-CD28 microclusters.Communications biology · 2025Article
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 5 countries.
Funding
Abstract
Current US Food and Drug Administration-approved chimeric antigen receptor (CAR) T cells harbor the T cell receptor (TCR)-derived ζ chain as an intracellular activation domain in addition to costimulatory domains. The functionality in a CAR format of the other chains of the TCR complex, namely CD3δ, CD3ε and CD3γ, instead of ζ, remains unknown. In the present study, we have systematically engineered new CD3 CARs, each containing only one of the CD3 intracellular domains. We found that CARs containing CD3δ, CD3ε or CD3γ cytoplasmic tails outperformed the conventional ζ CAR T cells in vivo. Transcriptomic and proteomic analysis revealed differences in activation potential, metabolism and stimulation-induced T cell dysfunctionality that mechanistically explain the enhanced anti-tumor performance. Furthermore, dimerization of the CARs improved their overall functionality. Using these CARs as minimalistic and synthetic surrogate TCRs, we have identified the phosphatase SHP-1 as a new interaction partner of CD3δ that binds the CD3δ-ITAM on phosphorylation of its C-terminal tyrosine. SHP-1 attenuates and restrains activation signals and might thus prevent exhaustion and dysfunction. These new insights into T cell activation could promote the rational redesign of synthetic antigen receptors to improve cancer immunotherapy.
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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.