ArticleNature immunology2020
Inefficient CAR-proximal signaling blunts antigen sensitivity.
Article in Nature immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 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
106 citing papers in PubMed, 158 citations in OpenAlex.
- Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma.Frontiers in immunology · 2022Trial
- Neutrophil-integrated syncytial CAR macrophage for cancer immunotherapy.Nature immunology · 2026Article
- Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.Signal transduction and targeted therapy · 2026Review
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- 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
- How crosstalk at the immune synapse shapes T cell and dendritic cell biology.Nature reviews. Immunology · 2026Review
- Structure-Function Insights into Immune Receptors Drive Innovation in CAR-T Cell Therapy.Current issues in molecular biology · 2026Review
- T-cell protrusions enable fast, localised initiation of chimeric antigen receptor signalling.The EMBO journal · 2026Article
- Transformative biomechanics and mechanobiology breakthroughs shaping the future of health and medicine.Innovation (Cambridge (Mass.)) · 2026Review
- IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.Nature chemical biology · 2026Article
- Intrinsically disordered domains expand the CAR T cell toolbox.Nature chemical biology · 2026Article
- Adaptation of lentiviral vectors for viral gene therapy and their impact on host cell biology.Journal of translational medicine · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- ImmTACs overcome cytotoxic T cell suppression.Immunotherapy advances · 2026Article
- Adoptive T Cell therapy for cancer and autoimmune disease: current advances, challenges, and future directions.Oncology reviews · 2026Article
- Enhancing CAR sensitivity through engineering of proximal signaling molecules.Nature cancer · 2025Article
- Engineering T cells with a membrane-tethered version of SLP-76 overcomes antigen-low resistance to CAR T cell therapy.Nature cancer · 2025Article
- Targeting the roots of myeloid malignancies with T cell receptors.Nature reviews. Cancer · 2025Review
- A yeast surface display platform for characterizing CAR T cell responses to cancer antigens.Nature communications · 2025Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Rational design of chimeric antigen receptors (CARs) with optimized anticancer performance mandates detailed knowledge of how CARs engage tumor antigens and how antigen engagement triggers activation. We analyzed CAR-mediated antigen recognition via quantitative, single-molecule, live-cell imaging and found the sensitivity of CAR T cells toward antigen approximately 1,000-times reduced as compared to T cell antigen-receptor-mediated recognition of nominal peptide-major histocompatibility complexes. While CARs outperformed T cell antigen receptors with regard to antigen binding within the immunological synapse, proximal signaling was significantly attenuated due to inefficient recruitment of the tyrosine-protein kinase ZAP-70 to ligated CARs and its reduced concomitant activation and subsequent release. Our study exposes signaling deficiencies of state-of-the-art CAR designs, which presently limit the efficacy of CAR T cell therapies to target tumors with diminished antigen expression.
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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.