ArticleCancer cell2015
Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells.
Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06879340 (A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies), which is not on this map. Cited by 568 papers, 1 of them a synthesis that pooled it.
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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.
A Phase 1 Multicenter, Open Label Trial Evaluating the Safety and Efficacy of DuoCAR20.19.22-D95 in Adult Patients With Relapsed or Refractory B-cell Malignancies
Who cites it
568 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Efficacy and safety of third-generation CD19-CAR T cells incorporating CD28 and TLR2 intracellular domains for B-cell malignancies with central nervous system involvement: results of a pivotal trial.Journal of translational medicine · 2025Trial
- Augmenting CAR T cell functionality and metabolism through CD39 downtuning.Molecular therapy. Oncology · 2026Article
- Review
- Tisa-cel and axi-cel CAR structure influences the development of resistance to CD19-CAR-T therapy.Leukemia · 2026Article
- C-terminal CD28 phosphorylation, pY218, modulates IL-2 secretion and therapeutic effect of CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Investigating the role of costimulatory domains in enhancing CAR-T cell persistence in TNBC.Cancer gene therapy · 2026Review
- AI-enabled discovery and biochemical optimization of minibinders targeting cancer cell-surface proteins.Nature communications · 2026Article
- Enhancing iNKT cell immunotherapy through the integration of optimized CAR endodomains and iNKT engagers.Nature communications · 2026Article
- Disruption of RBPJ in liver cancer-infiltrating T cells enhances antitumor immunity through remodeling epigenetic landscape.Cell death and differentiation · 2026Article
- Low-Strength Type I Interferon Signaling Promotes CAR T-cell Treatment Efficacy.Cancer immunology research · 2026Article
- The Role of Precision Medicine in Neuroblastoma: Targeted Therapies and Personalized Approaches-A Narrative Review.Health science reports · 2026Article
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- Metabolic and functional analysis including repetitive antigen stimulation provides a more accurate assessment for CAR-T cell product quality and long-term functionality.Journal of translational medicine · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- An ICAM1-Targeting Chimeric Costimulatory Receptor Mimics the Immune Synapse and Enhances Tumor-Specific T-cell Function.Cancer immunology research · 2026Article
- Fate induction through asymmetric T cell division is modulated by chimeric antigen receptor costimulatory domains.Nature immunology · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Genetic Code Expanded T Cell for Controllable Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- EZH2 and intracellular CaCellular & molecular immunology · 2026Article
508 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
T cell engineering is a powerful means to rapidly generate anti-tumor T cells. The costimulatory properties of second-generation chimeric antigen receptors (CARs) determine the overall potency of adoptively transferred T cells. Using an in vivo "stress test" to challenge CD19-targeted T cells, we studied the functionality and persistence imparted by seven different CAR structures providing CD28 and/or 4-1BB costimulation. One configuration, which uses two signaling domains (CD28 and CD3ζ) and the 4-1BB ligand, provided the highest therapeutic efficacy, showing balanced tumoricidal function and increased T cell persistence accompanied by an elevated CD8/CD4 ratio and decreased exhaustion. Remarkably, induction of the IRF7/IFNβ pathway was required for optimal anti-tumor activity. Thus, 1928z-41BBL T cells possess strikingly potent intrinsic and immunomodulatory qualities.
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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.