ArticleCell reports. Medicine2024
Development of a chimeric cytokine receptor that captures IL-6 and enhances the antitumor response of CAR-T cells.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- Chimeric IL-6/4R-LL37 Engineered Macrophages Achieve Synchronized Inflammation Control and Antimicrobial Defence in Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Engineered macrophages with IL-10-TLR9 signal switch receptors for reprogramming tumor microenvironment and enhancing antitumor immunity.Experimental & molecular medicine · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Synthetic cleavage-resistant TREM2 boosts macrophage efferocytosis to treat inflammatory diseases.Cell reports. Medicine · 2026Article
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Review
- Cytokine Engineering in CAR-T Cell Therapy: Next-Generation Strategies.Immune network · 2025Review
- Constructing the cure: engineering the next wave of antibody and cellular immune therapies.Journal for immunotherapy of cancer · 2025Review
- JAK-STAT-activated, fratricide-resistant CAR-T cells targeting membrane-bound TNF effectively treat AML and solid tumors.Journal for immunotherapy of cancer · 2025Article
- Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.Frontiers in immunology · 2025Review
- Toxicities Associated with CAR-T Cell Therapies.Mediterranean journal of hematology and infectious diseases · 2025Review
- Chimeric switch and inverted cytokine receptors in T cell therapy: reprogramming T cells to overcome immune suppression in the solid tumor microenvironment.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy is suboptimal in most cancers, necessitating further improvement in their therapeutic actions. However, enhancing antitumor T cell response inevitably confers an increased risk of cytokine release syndrome associated with monocyte-derived interleukin-6 (IL-6). Thus, an approach to simultaneously enhance therapeutic efficacy and safety is warranted. Here, we develop a chimeric cytokine receptor composed of the extracellular domains of GP130 and IL6RA linked to the transmembrane and cytoplasmic domain of IL-7R mutant that constitutively activates the JAK-STAT pathway (G6/7R or G6/7R-M452L). CAR-T cells with G6/7R efficiently absorb and degrade monocyte-derived IL-6 in vitro. The G6/7R-expressing CAR-T cells show superior expansion and persistence in vivo, resulting in durable antitumor response in both liquid and solid tumor mouse models. Our strategy can be widely applicable to CAR-T cell therapy to enhance its efficacy and safety, irrespective of the target antigen.
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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.