ArticleiScience2020
ERK Activation in CAR T Cells Is Amplified by CD28-Mediated Increase in CD3ζ Phosphorylation.
Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- A Systematic Review of the Efforts and Hindrances of Modeling and Simulation of CAR T-cell Therapy.The AAPS journal · 2021Pooled it
- Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- A multiscale, Bayesian inference approach to augment mechanistic models of cell signaling with machine-learning predictions of binding affinity.PLoS computational biology · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- A Newly Developed TGF-Β-Responsive CAR T Cell for Enhanced Proliferation and Cytokine Secretion.Advanced pharmaceutical bulletin · 2025Article
- Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation.Journal of translational medicine · 2025Review
- Accelerating CAR-T Cell Therapies with Small-Molecule Inhibitors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- A stochastic framework for evaluating CAR T cell therapy efficacy and variability.Mathematical biosciences · 2024Article
- Current advances in experimental and computational approaches to enhance CAR T cell manufacturing protocols and improve clinical efficacy.Frontiers in molecular medicine · 2024Review
- Information-Theoretic Analysis of a Model of CAR-4-1BB-Mediated NFκB Activation.Bulletin of mathematical biology · 2023Article
- Functional enhancement of mesothelin-targeted TRuC-T cells by a PD1-CD28 chimeric switch receptor.Cancer immunology, immunotherapy : CII · 2023Article
- PASCAR: a multiscale framework to explore the design space of constitutive and inducible CAR T cells.Life science alliance · 2023Article
- A data-driven Boolean model explains memory subsets and evolution in CD8+ T cell exhaustion.NPJ systems biology and applications · 2023Article
- Balancing activation and co-stimulation of CAR tunes signaling dynamics and enhances therapeutic potency.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Modelling predicts differences in chimeric antigen receptor T-cell signalling due to biological variability.Royal Society open science · 2022Article
- Mapping CAR T-Cell Design Space Using Agent-Based Models.Frontiers in molecular biosciences · 2022Article
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptors (CARs) are engineered receptors that mediate T cell activation. CARs are comprised of activating and co-stimulatory intracellular signaling domains derived from endogenous T cells that initiate signaling required for T cell activation, including ERK activation through the MAPK pathway. Understanding the mechanisms by which co-stimulatory domains influence signaling can help guide the design of next-generation CARs. Therefore, we constructed an experimentally validated computational model of anti-CD19 CARs in T cells bearing the CD3ζ domain alone or in combination with CD28. We performed a systematic analysis to explore the different mechanisms of CD28 co-stimulation on the ERK response time. Comparing these model simulations with experimental data indicates that CD28 primarily influences ERK activation by enhancing the phosphorylation kinetics of CD3ζ. Overall, we present a mechanistic mathematical modeling framework that can be used to gain insights into the mechanism of CAR T cell activation and produce new testable hypotheses.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.