ArticleScience immunology2022
Size-dependent activation of CAR-T cells.
Article in Science immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 115 citations in OpenAlex.
- Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx.bioRxiv : the preprint server for biology · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Multiple Myeloma Cells Resistant to T-cell Therapies Exhibit a CD45+ Immunoevasive Phenotype.Cancer immunology research · 2026Article
- Mapping and engineering the human cell-cell interactome.Nature biotechnology · 2026Review
- CD45 as a multifunctional target in immune regulation and therapeutic delivery.Journal of translational medicine · 2026Review
- How crosstalk at the immune synapse shapes T cell and dendritic cell biology.Nature reviews. Immunology · 2026Review
- Spatial Regulation of CAR Signaling Enables Logic-Gated Activity.bioRxiv : the preprint server for biology · 2026Article
- T-cell protrusions enable fast, localised initiation of chimeric antigen receptor signalling.The EMBO journal · 2026Article
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Rapid CAR screening and circRNA-driven CAR-NK cells for persistent shed-resistant immunotherapy.Signal transduction and targeted therapy · 2026Article
- Real-time multimodal phenotyping reveals distinct tumour cell dynamics and immune escape mechanisms in T cell therapies.Nature biomedical engineering · 2026Article
- Enzymatic Remodelling of Tumour Microenvironment Enhances Anti-CEACAM5 CAR T-Cell Efficacy Against Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IDR-induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers.Nature chemical biology · 2026Article
- Chimeric antigen receptor T‑cell therapy in chronic viral infections: a review.Journal of translational medicine · 2026Review
- CAR-T cell signaling dynamics, rational design principles and artificial intelligence for next-generation chimeric antigen receptors.Frontiers in immunology · 2026Review
- BAFF-based trifunctional T-cell engagers trigger robust tumor immunity against B-cell malignancies.Protein & cell · 2025Article
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- Emerging strategies in CAR-T cell therapy for acute myeloid leukemia: overcoming heterogeneity and improving safety through dual-antigen targeting.Experimental hematology & oncology · 2025Review
- A yeast surface display platform for characterizing CAR T cell responses to cancer antigens.Nature communications · 2025Article
- Conversion of natural cytokine receptors into orthogonal synthetic biosensors.Nature chemical biology · 2025Article
24 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 3 institutions in 1 country.
Funding
Abstract
As the targets of chimeric antigen receptor (CAR)-T cells expand to a variety of cancers, autoimmune diseases, viral infections, and fibrosis, there is an increasing demand for identifying new antigens and designing new CARs that can be effectively activated. However, the rational selection of antigens and the design of CARs are limited by a lack of knowledge regarding the molecular mechanism by which CARs are activated by antigens. Here, we present data supporting a "size exclusion" model explaining how antigen signals are transmitted across the plasma membrane to activate the intracellular domains of CARs. In this model, antigen engagement with CAR results in a narrow intermembrane space that physically excludes CD45, a bulky phosphatase, out of the CAR zone, thus favoring CAR phosphorylation by kinases, which further triggers downstream pathways leading to T cell activation. Aligned with this model, increasing the size of CAR extracellular domains diminished CAR-T activation both in vitro and in a mouse lymphoma model; membrane-proximal epitopes activated CAR-Ts better than membrane-distal epitopes. Moreover, increasing the size of CD45 by antibody conjugation enhanced the activation of CARs that recognize membrane-distal epitopes. Consistently, CAR-Ts expressing CD45RABC, the larger isoform, were activated to a higher level than those expressing a smaller isoform CD45RO. Together, our work revealed that CAR-T activation depends on the size difference between the CAR-antigen pair and CD45; the size of CAR, antigen, and CD45 can thus be targets for tuning CAR-T activation.
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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.