ArticleCell biology and toxicology2023
GPC3-IL7-CCL19-CAR-T primes immune microenvironment reconstitution for hepatocellular carcinoma therapy.
Article in Cell biology and toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 46 citations in OpenAlex.
- Autocrine PD-1-blocking nanobodies enhance the antitumor efficacy of TCR-like CAR-T cells by attenuating t cell exhaustion.Journal of translational medicine · 2026Article
- Glypican-3-targeted therapy in hepatocellular carcinoma: biological insights and therapeutic strategies.Cancer gene therapy · 2026Review
- Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.Biomarker research · 2026Review
- Progress in the development of cytokine armoured CAR T cells.Nature reviews. Immunology · 2026Review
- A review of organoid-immune co-culture platforms to model the immune microenvironment of hepatocellular carcinoma and guide immunotherapy.Journal of translational medicine · 2026Review
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- Organoids: technology refining, current applications and future directions.Molecular biomedicine · 2026Review
- Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates.Seminars in liver disease · 2026Review
- Advances and challenges of chimeric antigen receptor T cell therapy in digestive system malignancies.World journal of clinical oncology · 2026Review
- Organoid models for T cell-based immunotherapy in hepatobiliary cancers.Hepatobiliary surgery and nutrition · 2025Article
- Immune checkpoint biology in hepatocellular carcinoma (Review).Oncology letters · 2025Review
- Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.Gut microbes · 2025Review
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- The challenges and progress of CAR-T cell therapy in the treatment of solid tumors.Molecular and cellular biochemistry · 2025Review
- Establishment of a prognostic model and immune profiling based on phagocytic regulatory genes in hepatocellular carcinoma.Translational cancer research · 2025Article
- Targeting glypican-3 as a new frontier in liver cancer therapy.World journal of hepatology · 2025Review
- Targeting Glypican-3 for Liver Cancer Therapy: Clinical Applications and Detection Methods.Journal of clinical and translational hepatology · 2025Review
- T lymphocyte-based immune response and therapy in hepatocellular carcinoma: focus on TILs and CAR-T cells.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- hCCL19-expressing recombinant Newcastle disease virus boosts CAR T cell infiltration and efficacy in solid tumor.Journal for immunotherapy of cancer · 2025Article
- Effect of anti-CD4 mAb induced by inhibiting B cell disorder on immune reconstruction of HIV-infected immunological non-responders.Molecular medicine (Cambridge, Mass.) · 2025Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor (CAR)-T-cell therapy is a revolutionary treatment that has become a mainstay of advanced cancer treatment. Conventional glypican-3 (GPC3)-CAR-T cells have not produced ideal clinical outcomes in advanced hepatocellular carcinoma (HCC), and the mechanism is unclear. This study aims to investigate the clinical utility of novel GPC3-7-19-CAR-T cells constructed by our team and to explore the mechanisms underlying their antitumor effects.
methodsWe engineered a novel GPC3-targeting CAR including an anti-GPC3 scFv, CD3ζ, CD28 and 4-1BB that induces co-expression of IL-7 at a moderate level (500 pg/mL) and CCL19 at a high level (15000 pg /mL) and transduced it into human T cells. In vitro, cell killing efficacy was validated by the xCELLigence RTCA system, LDH nonradioactive cytotoxicity assay and was confirmed in primary HCC organoid models employing a 3D microfluid chip. In vivo, the antitumor capacity was assessed in a humanized NSG mouse xenograft model. Finally, we initiated a phase I clinical trial to evaluate the safety and effect of GPC3-7-19-CAR-T cells in the clinic.
resultsGPC3-7-19-CAR-T cells had 1.5-2 times higher killing efficiency than GPC3-CAR-T cells. The tumor formation rates in GPC3-7-19-CAR-T cells treated model were reduced (3/5vs.5/5), and the average tumor volumes were 0.74 cm
conclusionsIn conclusion, GPC3-7-19-CAR-T cells achieved antitumor effects superior to those of conventional GPC3-CAR-T cells by reconstructing the TME induced by the dominant CD4
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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.