ArticleNAR cancer2024
Codelivery of TGFβ and Cox2 siRNA inhibits HCC by promoting T-cell penetration into the tumor and improves response to Immune Checkpoint Inhibitors.
Article in NAR cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
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- Targeting Lipid Metabolic Reprogramming to Overcome Immunotherapy Resistance: Systemic Nutritional Modulation and Precision Nanomedicine.International journal of nanomedicine · 2026Review
- Polymeric Nanomedicines for siRNA Delivery in Hepatocellular Carcinoma: Emerging Therapeutic Strategies, Combination Approaches, and Translational Perspectives.International journal of nanomedicine · 2026Review
- Review
- Recent advances in gene delivery for melanocyte-associated disorders.Advanced drug delivery reviews · 2025Review
- Advances in RNA-based cancer therapeutics: pre-clinical and clinical implications.Molecular cancer · 2025Review
- Targeting tumor immune evasion: the role of PD-L1 siRNA in advancing cancer immunotherapy.Medical oncology (Northwood, London, England) · 2025Review
- The Roles of SHCBP1 in Cancer Hallmarks: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Current and Emerging Insights into the Causes, Immunopathogenesis, and Treatment of Cutaneous Squamous Cell Carcinoma.Cancers · 2025Review
- siRNA tackles cancer: Immune checkpoint inhibitors and siRNA combinations.Molecular therapy. Nucleic acids · 2025Article
- Advanced Nanotechnology-Based Nucleic Acid Medicines.Pharmaceutics · 2024Review
- Exploring the therapeutic potential ofEXCLI journal · 2024Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upregulation of TGFβ and Cox2 in the tumor microenvironment results in blockade of T-cell penetration into the tumor. Without access to tumor antigens, the T-cell response will not benefit from administration of the immune checkpoint antibodies. We created an intravenous polypeptide nanoparticle that can deliver two siRNAs (silencing TGFβ and Cox2). Systemic administration in mice, bearing a syngeneic orthotopic hepatocellular carcinoma (HCC), delivers the siRNAs to various cells in the liver, and significantly reduces the tumor. At 2 mg/kg (BIW) the nanoparticle demonstrated a single agent action and induced tumor growth inhibition to undetectable levels after five doses. Reducing the siRNAs to 1mg/kg BIW demonstrated greater inhibition in the presence of PD-L1 mAbs. After only three doses BIW, we could still recover a smaller tumor and, in tumor sections, showed an increase in penetration of CD4+ and CD8+ T-cells deeper into the remaining tumor that was not evident in animals treated with non-silencing siRNA. The combination of TGFβ and Cox2 siRNA co-administered in a polypeptide nanoparticle can act as a novel therapeutic alone against HCC and may augment the activity of the immune checkpoint antibodies. Silencing TGFβ and Cox2 converts an immune excluded (cold) tumor into a T-cell inflamed (hot) tumor.
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