ArticleScience signaling2021
Comparative analysis of TCR and CAR signaling informs CAR designs with superior antigen sensitivity and in vivo function.
Article in Science signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- The safety and efficacy of chimeric antigen receptor-T cell therapy in solid malignancies: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Adoptive cell therapies in thoracic malignancies: a comprehensive review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial.Nature medicine · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Humanized biparatopic nanobody-based CAR-T cells overcome antigen-heterogeneity in multiple myeloma.Journal of translational medicine · 2026Article
- Chimeric switch scaffold protein augments CAR synapse formation and signaling networks.Journal for immunotherapy of cancer · 2026Article
- Engagement of the TCR against an oncolytic virus generates a population of effector CAR T cells with potent antitumor activity.Science advances · 2026Article
- T-cell protrusions enable fast, localised initiation of chimeric antigen receptor signalling.The EMBO journal · 2026Article
- Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma.Blood neoplasia · 2026Article
- mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression.Nature biotechnology · 2026Article
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- Phosphotyrosine proteomics reveals novel Zap70 and Itk pathway targets downstream of TCR and CAR in Jurkat T cells.Scientific reports · 2026Article
- FcεRγI promotes canine CD8 chimeric antigen receptor T cell cytotoxicity through a Syk-NF-κB axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Ready or not, here they come: a practical guide to adoptive T-cell therapies for solid tumors for medical oncologists.The oncologist · 2026Review
- IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.Nature chemical biology · 2026Article
- Phosphoproteomic analysis of successive Jurkat CD19-CAR generations reveals TCRζ-driven signalling.Cellular signalling · 2026Article
- Optimally engineered HLA/peptide-specific CAR-T cells outperform TCR-T cells to eradicate solid tumors.Science advances · 2026Article
- Engineering Immunity: Current Progress and Future Directions of CAR-T Cell Therapy.International journal of molecular sciences · 2026Review
- The safety and efficacy of GD2-targeted CAR-T cells in patients with neuroblastoma: a systematic review and meta-analysis.European journal of medical research · 2026Review
49 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
15 authors at 3 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR)-modified T cell therapy is effective in treating lymphomas, leukemias, and multiple myeloma in which the tumor cells express high amounts of target antigen. However, achieving durable remission for these hematological malignancies and extending CAR T cell therapy to patients with solid tumors will require receptors that can recognize and eliminate tumor cells with a low density of target antigen. Although CARs were designed to mimic T cell receptor (TCR) signaling, TCRs are at least 100-fold more sensitive to antigen. To design a CAR with improved antigen sensitivity, we directly compared TCR and CAR signaling in primary human T cells. Global phosphoproteomic analysis revealed that key T cell signaling proteins-such as CD3δ, CD3ε, and CD3γ, which comprise a portion of the T cell co-receptor, as well as the TCR adaptor protein LAT-were either not phosphorylated or were only weakly phosphorylated by CAR stimulation. Modifying a commonplace 4-1BB/CD3ζ CAR sequence to better engage CD3ε and LAT using embedded CD3ε or GRB2 domains resulted in enhanced T cell activation in vitro in settings of a low density of antigen, and improved efficacy in in vivo models of lymphoma, leukemia, and breast cancer. These CARs represent examples of alterations in receptor design that were guided by in-depth interrogation of T cell signaling.
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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.