ArticleGastroenterology2020
Persistent Polyfunctional Chimeric Antigen Receptor T Cells That Target Glypican 3 Eliminate Orthotopic Hepatocellular Carcinomas in Mice.
Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 117 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Targeted Therapies for Hepatocellular Carcinoma Treatment: A New Era Ahead-A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial.Oncoimmunology · 2020Trial
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?Nature reviews. Clinical oncology · 2026Article
- Engineering CAR T Cells for Hepatocellular Carcinoma Recurrence after Liver Transplantation.bioRxiv : the preprint server for biology · 2026Article
- A Review of Recent Advances in Chimeric Antigen Receptor (CAR) T-Cell Therapy for Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Granzyme B-based CAR-T cells targeting membrane-bound HSP70 suppress solid tumor growth and metastasis.Oncogene · 2026Article
- Allogeneic CRISPR-Engineered CAR-T Cells Drive Potent Antitumor Activity in Solid Tumors.bioRxiv : the preprint server for biology · 2026Article
- Engineered outer membrane vesicles enhance solid tumour CAR-T cell therapy.Nature biomedical engineering · 2026Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- An endoplasmic reticulum membrane-mimetic GPC3 mRNA nanovaccine for specific immunotherapy of hepatocellular carcinoma.Communications biology · 2026Article
- Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates.Seminars in liver disease · 2026Review
- Targeting epigenetic regulators to boost T cell immunotherapy against cancer.Cell & bioscience · 2026Review
- Preclinical development of mesothelin-targeting CAR T cells for the treatment of cholangiocarcinoma.Hepatology communications · 2026Article
- CAR-T triggers TAM reeducation and adaptive anti-tumor response via TREM2 deficiency or CD40 agonist.Cell reports. Medicine · 2026Article
- Identification of tumor-associated antigens with multi-cancer therapeutic potential.Frontiers in immunology · 2026Article
- Diagnosis and Treatment Response Monitoring of Liver Cancer Using Glypican-3-Targeted Single-Domain Antibody PET.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- 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
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- Hypoxia-mediated mJournal of translational medicine · 2025Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrection.2021
Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsGlypican 3 (GPC3) is an oncofetal antigen involved in Wnt-dependent cell proliferation that is highly expressed in hepatocellular carcinoma (HCC). We investigated whether the functions of chimeric antigen receptors (CARs) that target GPC3 are affected by their antibody-binding properties.
methodsWe collected peripheral blood mononuclear cells from healthy donors and patients with HCC and used them to create CAR T cells, based on the humanized YP7 (hYP7) and HN3 antibodies, which have high affinities for the C-lobe and N-lobe of GPC3, respectively. NOD/SCID/IL-2Rgc
resultsInjections of CAR (hYP7) T cells eliminated tumors in 66% of mice by week 3, whereas CAR (HN3) T cells did not reduce tumor burden. Mice given CAR (hYP7) T cells remained tumor free after re-challenge with additional Hep3B cells. The CAR T cells induced perforin- and granzyme-mediated apoptosis and reduced levels of active β-catenin in HCC cells. Mice injected with CAR (hYP7) T cells had persistent expansion of T cells and subsets of polyfunctional CAR T cells via antigen-induced selection. These T cells were observed in the tumor microenvironment and spleen for up to 7 weeks after CAR T-cell administration. Integration sites in pre-infusion CAR (HN3) and CAR (hYP7) T cells were randomly distributed, whereas integration into NUPL1 was detected in 3.9% of CAR (hYP7) T cells 5 weeks after injection into tumor-bearing mice and 18.1% of CAR (hYP7) T cells at week 7. There was no common site of integration in CAR (HN3) or CD19 CAR T cells from tumor-bearing mice.
conclusionsIn mice with xenograft or orthoptic liver tumors, CAR (hYP7) T cells eliminate GPC3-positive HCC cells, possibly by inducing perforin- and granzyme-mediated apoptosis or reducing Wnt signaling in tumor cells. GPC3-targeted CAR T cells might be developed for treatment of patients with HCC.
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Registered trials
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.