ArticleHepatology (Baltimore, Md.)2025
GPC3-based circular RNA vaccine suppresses hepatocellular carcinoma progression by activating adaptive immune responses.
Article in Hepatology (Baltimore, Md.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Genome stability disrupted by the circRBM39(4,5,6)-RPA2 axis represses breast tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Research Progress, Application, and Industrialization Prospects of Circular RNA Vaccines in Viral Diseases.Vaccines · 2026Review
- Novel Insights into the Role of circRNAs in Cancer Immunotherapy Resistance and Clinical Implications.International journal of molecular sciences · 2026Review
- Lipid nanoparticle delivery of circle RNA vaccine induces potent immune responses.Scientific reports · 2026Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- mRNA processing in cancer immunotherapy: emerging targets, resistance mechanisms, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Functional roles and mechanisms of circRNA-protein interactions in cancer progression and tumor immune regulation.Frontiers in immunology · 2026Review
- Circular RNA in hepatocellular carcinoma: emerging therapeutic strategies.Frontiers in immunology · 2025Review
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsMessenger RNA (mRNA) vaccine is a promising approach for cancer therapy. However, the development of mRNA cancer vaccines encounters several challenges, including mRNA instability, inefficient delivery systems, and potential biosafety concerns. Addressing these issues requires optimizing mRNA design, developing novel delivery vectors, and enhancing immune responses. We aimed to develop a circular RNA (circRNA)-based cancer vaccine targeting tumor-associated antigen Glypican-3 (GPC3), a promising target in hepatocellular carcinoma (HCC), to improve antigen stability and anti-tumor immune responses. APPROACH AND
resultsWe designed a circRNA-based vaccine encoding GPC3 for HCC and evaluated the therapeutic efficacy and safety of the circGPC3 vaccine. The circGPC3 vaccine demonstrated sustained antigen production, overcoming the inherent limitations of traditional mRNA vaccines and resulting in more potent and durable anti-tumor immune responses. In addition, we incorporated a Toll-like receptor 4 (TLR4) agonist as an adjuvant to further enhance immune responses. CircGPC3 vaccine plus TLR4 agonist effectively suppressed tumor progression in HCC. We employed multiplex immunofluorescence, single-cell sequencing, spatial transcriptomics, and mass cytometry to characterize the tumor microenvironment (TME) in mice following combination therapy and to elucidate the mechanism. Mechanistically, the circGPC3 vaccine significantly enhanced immunoproteasome-mediated antigen presentation and strengthened the interaction between cDC1 and CD8 + T cells through the MHC-I pathway, therefore facilitating a more effective initiation of adaptive immune responses and reprogramming TME.
conclusionsThe circGPC3 cancer vaccine demonstrated superior efficacy compared with the mRNA cancer vaccine. When further combined with a TLR4 agonist, it disrupted immune tolerance in HCC, offering a promising translational treatment strategy for HCC.
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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.