ArticleScience immunology2023
CD19 CAR antigen engagement mechanisms and affinity tuning.
Article in Science immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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
51 citing papers in PubMed.
- Fine-tuning affinity and spacer design enhances T cell potency in DLL3 and BCMA CAR T cells.mAbs · 2026Article
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Tisa-cel and axi-cel CAR structure influences the development of resistance to CD19-CAR-T therapy.Leukemia · 2026Article
- Article
- Perspective for CAR T-Cell Therapy in Underrepresented Populations: A Hypothesis-Generating CD19 Genomic Analysis.Journal of personalized medicine · 2026Article
- Structural dissection of CD38 antigen engagement by CAR binders and rational affinity tuning.iScience · 2026Article
- Trogocytosis in cancer immunity and cellular immunotherapy: mechanisms, therapeutic challenges, and translational opportunities.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Programmable macromolecule delivery via engineered trogocytosis.Nature cell biology · 2026Article
- Targeting the pMHC-TCR Interaction: Molecular Strategies and Therapeutic Potential in Autoimmunity.International journal of molecular sciences · 2026Review
- Balancing the efficacy and safety of chimeric antigen receptor T-cell therapy by affinity combination.Nature communications · 2026Article
- Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells.Nature biomedical engineering · 2026Article
- Targeting GPA33 with CAR-macrophages: a novel immunotherapeutic approach for colorectal cancer.Journal of translational medicine · 2026Article
- Dynamic, single-cell monitoring of CAR T cell identity and activation with Raman spectroscopy.bioRxiv : the preprint server for biology · 2026Article
- Tumor-Associated Macrophages as Therapeutic Targets: Deciphering Interaction Networks and Advancing Clinical Translation.MedComm · 2026Review
- The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Selective Immune Silencing by Targeted TGF-β Agonists.bioRxiv : the preprint server for biology · 2026Article
- Resistance mechanisms and overcoming strategies for CAR T-cell therapy in B-cell hematologic malignancies.Frontiers in immunology · 2026Review
- CD19-negative relapse after CAR-T cell therapy: mechanisms of antigen escape and lineage switch.Frontiers in immunology · 2026Review
- CD19 exon 2 skipping is a potential prognostic correlate of anti-CD19 CAR-T therapy relapse.Frontiers in molecular medicine · 2026Article
- Development of production methodologies for scFv-Fc conjugated critical reagents to support CAR-T clinical programs.Bioanalysis · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy relies on T cells that are guided by synthetic receptors to target and lyse cancer cells. CARs bind to cell surface antigens through an scFv (binder), the affinity of which is central to determining CAR T cell function and therapeutic success. CAR T cells targeting CD19 were the first to achieve marked clinical responses in patients with relapsed/refractory B cell malignancies and to be approved by the U.S. Food and Drug Administration (FDA). We report cryo-EM structures of CD19 antigen with the binder FMC63, which is used in four FDA-approved CAR T cell therapies (Kymriah, Yescarta, Tecartus, and Breyanzi), and the binder SJ25C1, which has also been used extensively in multiple clinical trials. We used these structures for molecular dynamics simulations, which guided creation of lower- or higher-affinity binders, and ultimately produced CAR T cells endowed with distinct tumor recognition sensitivities. The CAR T cells exhibited different antigen density requirements to trigger cytolysis and differed in their propensity to prompt trogocytosis upon contacting tumor cells. Our work shows how structural information can be applied to tune CAR T cell performance to specific target antigen densities.
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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.