ArticleScience advances2025
Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- FATP2-mediated lipid metabolism enhances chimeric antigen receptor T-cell therapy resistance in B-cell acute lymphoblastic leukemia.Leukemia · 2026Article
- High-Precision Intrinsic Interactome Elucidation of Chimeric Antigen Receptors via Photocatalytic Micromapping (μMap-CAR).Journal of the American Chemical Society · 2026Article
- Chimeric switch scaffold protein augments CAR synapse formation and signaling networks.Journal for immunotherapy of cancer · 2026Article
- How crosstalk at the immune synapse shapes T cell and dendritic cell biology.Nature reviews. Immunology · 2026Review
- 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
- RASA2 deletion rescues immune synapse dysfunction, enhancing CAR T cell efficacy against DMGs.Journal for immunotherapy of cancer · 2026Article
- 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
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- TIGIT Affects CAR NK-cell Effector Function in the Solid Tumor Microenvironment by Modulating Immune Synapse Strength.Cancer immunology research · 2025Article
- Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas.Cancer immunology research · 2025Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART. We reasoned that molecular dynamics at the CART immune synapse (CARIS) could explain differences in their tumor rejection kinetics. We observed that CD28.ζ-CART engaged in brief highly lethal CARIS and mastered serial killing, whereas 4-1BB.ζ-CART formed lengthy CARIS and relied on robust expansion and cooperative killing. We analyzed CARIS membrane lipid rafts (mLRs) and found that, upon tumor engagement, CD28.ζ-CAR molecules rapidly but transiently translocated into mLRs, mobilizing the microtubular organizing center and lytic granules to the CARIS. This enabled fast CART recovery and sensitivity to low target site density. In contrast, gradual accumulation of 4-1BB.ζ-CAR and LFA-1 molecules at mLRs built mechanically tonic CARIS mediating chronic Fas ligand-based killing. The differences in CD28.ζ- and 4-1BB.ζ-CARIS dynamics explain the distinct cytolytic behavior of CART and can guide engineering of more adaptive effective cellular products.
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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.