ArticleJournal for immunotherapy of cancer2025
Co-expression of IL-15 and CCL21 strengthens CAR-NK cells to eliminate tumors in concert with T cells and equips them with PI3K/AKT/mTOR signal signature.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed.
- Natural Killer Cells: Dual Regulators and Therapeutic Targets in Multiple Sclerosis Immunopathogenesis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Smart responsive hydrogels combined with AI design for tumor therapy.Acta pharmaceutica Sinica. B · 2026Review
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- Review
- NK cell biomimetic MOF nanoplatform disrupts hypoxia adaption for complete tumor ablation.Journal of nanobiotechnology · 2026Article
- PD‑L1 deficient exosomes derived from lung cancer cell line enhances NK cell‑mediated anti‑tumor immunity against lung cancer.Cell communication and signaling : CCS · 2026Article
- Immune regulatory mechanisms in the tumor microenvironment and their applications in cancer therapy: from basic research to clinical translation.Frontiers in immunology · 2026Review
- Chimeric Antigen Receptor T Cells as Living Therapeutics Targeting Senescence and Age-Related Diseases.Research (Washington, D.C.) · 2026Review
- The Nanoparticle Delivery Gap in Immune Cell Engineering: From Uptake to Endosomal Escape.International journal of nanomedicine · 2026Review
- Expanding Immunotherapy Beyond CAR T Cells: Engineering Diverse Immune Cells to Target Solid Tumors.Cancers · 2025Review
- Co-expression of IL-15 and CCL21 strengthens CAR-NK cells to eliminate tumors in concert with T cells and equips them with PI3K/AKT/mTOR signal signature.Journal for immunotherapy of cancer · 2025Article
- Signaling intact membrane-bound IL-15 enables potent anti-tumor activity and safety of CAR-NK cells.Frontiers in immunology · 2025Article
- Enhancing the physiological characteristics of chimeric antigen receptor natural killer cells by synthetic biology.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor (CAR)-natural killer (NK) cell therapy has demonstrated safety and feasibility in clinical settings; however, limited efficacy due to intrinsic dysfunction and extrinsic suppression remains an unresolved issue. T cells provide multifaceted support to NK cell-mediated responses. Here, we aimed to design a novel CD19-targeted CAR-NK, engineered with secreted interleukin-15 and C-C motif chemokine ligand 21 (ie, 15×21 CAR-NK), capable of recruiting and cooperating with T cells.
methodsWe characterized 15×21 CAR-NK cells by performing experiments in vitro and in mouse models, and conducting RNA sequencing.
results15×21 CAR-NK cells exhibit strong capabilities in cytotoxicity, cytokine production, effector molecule expression, and T-cell recruitment in vitro. Cooperation with T cells promoted efficient tumor-cell elimination, alleviated mutual exhaustion phenotypes, and enhanced the expression of effector molecules/receptors. The recruitment and cooperative effects also result in effective tumor control in mouse models. In addition, 15×21 CAR-NK cells strongly enrich the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway - a key intracellular signaling cascade that is associated with enhanced downstream pro-survival signaling, anti-apoptotic ability, mitochondrial function, and cytotoxicity.
conclusionsOur study highlights the intrinsic advantages and extrinsic T-cell cooperative benefits of 15×21 CAR-NK cells, providing a promising strategy for NK-cell-based immunotherapy.
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