ArticleScience advances2025
Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screens and single-cell sequencing.
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 9 papers, 1 of them a synthesis that pooled it.
What it found
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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
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- CAR-T cell signaling dynamics, rational design principles and artificial intelligence for next-generation chimeric antigen receptors.Frontiers in immunology · 2026Review
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- Predictive markers for the efficacy of CAR T-cell therapy: the interplay between CAR T-cell fitness and systemic immunity.Blood advances · 2025Review
- Rewiring T Cell Metabolism to Enhance CAR T Cell Function in Solid Tumor Microenvironments.Pharmaceutics · 2025Review
- CD28 signaling complexes are correlated with patient outcomes in anti-CD19 41BB-costimulation CAR T cell therapy.Journal for immunotherapy of cancer · 2025Article
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Pooled screening for CAR function identifies novel IL-13Rα2-targeted CARs for treatment of glioblastoma.Journal for immunotherapy of cancer · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cells offer a promising cancer treatment, yet challenges such as limited T cell persistence hinder efficacy. Given its critical role in modulating T cell responses, it is crucial to understand how the CAR signaling architecture influences T cell function. Here, we designed a combinatorial CAR signaling domain library and performed repeated antigen stimulation assays, pooled screens, and single-cell sequencing to systematically investigate the impact of modifying CAR signaling domains on T cell activation and persistence. Our data reveal the predominant influence of membrane-proximal domains in driving T cell phenotype. Notably, CD40 costimulation was crucial for fostering robust and lasting T cell responses. Furthermore, we correlated in vitro generated CAR T cell phenotypes with clinical outcomes in patients treated with CAR T therapy, establishing the foundation for a clinically informed screening approach. This work deepens our understanding of CAR T cell biology and may guide future CAR engineering efforts.
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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.