ArticleClinical and experimental medicine2024
IL-21- and CXCL9-engineered GPC3-specific CAR-T cells combined with PD-1 blockade enhance cytotoxic activities against hepatocellular carcinoma.
Article in Clinical and experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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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
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Glypican-3-targeted bioconjugates for hepatocellular carcinoma: design, engineering, and translational applications.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- PVR Mediates Resistance to IL21.CD276.CAR-T Therapy in Esophageal Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- Safety and efficacy of JWATM204, a novel Glypican-3 (GPC3)-targeted CAR T cell therapy for advanced hepatocellular carcinoma: A phase I dose-escalation study.Cancer pathogenesis and therapy · 2026Article
- Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Impact of IL-21 on CAR T-cell manufacturing: phenotypic, metabolic, and functional outcomes.Frontiers in immunology · 2026Article
- Glypican-3-Specific CAR NK Cells Co-Secreting IL-15 and IFN-α Have Increased Anti-Tumor Function Versus Hepatocellular Carcinoma In Vitro.International journal of molecular sciences · 2025Article
- Targeting glypican-3 as a new frontier in liver cancer therapy.World journal of hepatology · 2025Review
- Interleukin 21-Armed EGFR-VHH-CAR-T Cell Therapy for the Treatment of Esophageal Squamous Cell Carcinoma.Biomedicines · 2025Article
- Tonic signaling in CAR-T therapy: the lever long enough to move the planet.Frontiers of medicine · 2025Review
- Exploration of the role of immune cells and cell therapy in hepatocellular carcinoma.Frontiers in immunology · 2025Review
- Glypican 3-targeted chimeric antigen receptor T cells secreting TROP2-directed bispecific T cell engagers exhibit potent efficacy against lung squamous cell carcinoma.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The application of CAR-T cells in solid tumors poses several challenges, including poor T cell homing ability, limited infiltration of T cells and an immunosuppressive tumor environment. In this study, we developed a novel approach to address these obstacles by designing GPC3-specific CAR-T cell that co-express IL-21 and CXCL9 (21 × 9 GPC3 CAR-T cells) and blocking the PD-1 expression on it. The proliferation, cell phenotype, cytokine secretion and cell migration of indicated CAR-T cells were evaluated in vitro. The cytotoxic activities of genetically engineered CAR-T cells were accessed in vitro and in vivo. Compared to conventional GPC3 CAR-T cells, the 21 × 9 GPC3 CAR-T cells demonstrated superior proliferation, cytokine secretion and chemotaxis capabilities in vitro. Furthermore, when combined with PD-1 blockade, the 21 × 9 GPC3 CAR-T cells exhibited enhanced proliferation, cytokine secretion and enrichment of effector T cells such as CTL, NKT and TEM cells. In xenograft tumor models, the PD-1 blocked 21 × 9 GPC3 CAR-T cells effectively suppressed HCC xenograft growth and increased T cell infiltration. Overall, our study successfully generated GPC3 CAR-T cells expressing both IL-21 and CXCL9, demonstrated that combining PD-1 blockade can further enhance CAR-T cell function by promoting proliferation, cytokine secretion, chemotaxis and antitumor activity. These findings present a hopeful and potentially effective strategy for GPC3-positive HCC patients.
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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 OpenQuestion graph.