ArticleProceedings of the National Academy of Sciences of the United States of America2023
Combined disruption of T cell inflammatory regulators Regnase-1 and Roquin-1 enhances antitumor activity of engineered human T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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.
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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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- 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
- The regnase family in autoimmune diseases: a regnase-1-centered perspective on cellular heterogeneity.Molecular biology reports · 2026Review
- High ZFP36 Family Expression in Exhausted T Cells Is Associated With Impaired Antitumor Effector Function.Cancer science · 2026Article
- Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.Cell reports. Medicine · 2026Article
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- Article
- RNA-binding proteins and ribonucleoproteins as determinants of immunity.Nature reviews. Immunology · 2026Review
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- A 3D multi-compartment assembloid to study combined immune cell infiltration and cytotoxicity.Cell reports methods · 2026Article
- CISH, a key intracellular checkpoint, in comparison and combination to existing and emerging cancer immune checkpoints.Communications biology · 2026Article
- The Regnase pathway: a core axis in immune regulation and inflammatory disease.Frontiers in immunology · 2026Review
- Research on the Mechanism of "Cold Tumor" Formation and Immunotherapy for Its Transformation into "Hot Tumor".Oncology research · 2026Review
- Rewriting CAR-T cell fate: CRISPR/Cas gene editing for solid tumor therapy.Frontiers in immunology · 2026Review
- CRISPR-screen informed engineered T cell therapies.Frontiers in immunology · 2026Review
- Orthogonal CRISPR systems for targeted integration and multiplex base editing enable nonviral engineering of allogeneic CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting RNA-Binding proteins Roquin-1 and Regnase-1 could enhance CAR-iPSC-derived macrophage immunotherapy for solid tumors: a perspective and challenges.RNA biology · 2025Article
- Manufacturing of CRISPR-edited primary mouse CAR T cells for cancer immunotherapy.Nature protocols · 2025Article
- Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.Nature reviews. Clinical oncology · 2025Review
- CAR-T cells in solid tumors: Challenges and breakthroughs.Cell reports. Medicine · 2025Review
- ZC3H12A: A Critical Mediator of Inflammation, Tumor Immunotherapy, and Metabolic-Immune Crosstalk-Implications for Disease Treatment.Biomolecules · 2025Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
A fundamental limitation of T cell therapies in solid tumors is loss of inflammatory effector functions, such as cytokine production and proliferation. Here, we target a regulatory axis of T cell inflammatory responses, Regnase-1 and Roquin-1, to enhance antitumor responses in human T cells engineered with two clinical-stage immune receptors. Building on previous observations of Regnase-1 or Roquin-1 knockout in murine T cells or in human T cells for hematological malignancy models, we found that knockout of either Regnase-1 or Roquin-1 alone enhances antitumor function in solid tumor models, but that knockout of both Regnase-1 and Roquin-1 increases function further than knockout of either regulator alone. Double knockout of Regnase-1 and Roquin-1 increased resting T cell inflammatory activity and led to at least an order of magnitude greater T cell expansion and accumulation in xenograft mouse models, increased cytokine activity, and persistence. However double knockout of Regnase-1 and Roguin-1 also led to a lymphoproliferative syndrome and toxicity in some mice. These results suggest that regulators of immune inflammatory functions may be interesting targets to modulate to improve antitumor responses.
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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.