ArticleHuman gene therapy2017
Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity.
Article in Human gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
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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
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- The immunotherapy advancement targeting malignant blastomas in early childhood.Frontiers in oncology · 2023Pooled it
- Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study.Leukemia · 2024Trial
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Genome-Wide Integration Site Profiling of Multi-Component CAR T-Cell Engineering Systems with ADA1/CD26 Co-Transduction.Biomedicines · 2026Article
- IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Plasma GPC3 reflects tumor GPC3 expression and predicts clinical outcomes in advanced HCC treated with atezolizumab + bevacizumab.JHEP reports : innovation in hepatology · 2026Article
- Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.Discover oncology · 2026Review
- Engineering CAR T NK and NKT cell therapies to target cancer stem cells and overcome stem like resistance.Discover oncology · 2025Review
- 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
- Hepatoblastoma.Nature reviews. Disease primers · 2025Review
- Enhanced cytotoxicity against cholangiocarcinoma by fifth-generation chimeric antigen receptor T cells targeting integrin αvβ6 and secreting anti-PD-L1 scFv.Journal of translational medicine · 2025Article
- Global, regional, and national epidemiology of hepatoblastoma in children from 1990 to 2021: a trend analysis.Hepatology international · 2025Article
- Recent advancements in improving the efficacy and safety of chimeric antigen receptor (CAR)-T cell therapy for hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Pediatric Hepatocellular Carcinoma: A Review of Predisposing Conditions, Molecular Mechanisms, and Clinical Considerations.International journal of molecular sciences · 2025Review
- Innovative applications of silicon dioxide nanoparticles for targeted liver cancer treatment.Frontiers in bioengineering and biotechnology · 2025Review
- Targeting archetypes of viral-driven cancers with immunotherapy: a perspective on immunogenicity within the tumor microenvironment.Frontiers in immunology · 2025Review
- Article
- Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression.Nature communications · 2024Article
- Treatment Options for Hepatocellular Carcinoma Using Immunotherapy: Present and Future.Journal of clinical and translational hepatology · 2024Review
- A novel lentiviral vector-based approach to generate chimeric antigen receptor T cells targetingmBio · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies. However, similar therapeutic efficacy of CAR T cells in solid tumors is yet to be achieved. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3ζ (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz). All GPC3-CARs rendered T cells highly cytotoxic to GPC3-positive hepatocellular carcinoma, hepatoblastoma, and malignant rhabdoid tumor cell lines in vitro. GBBz induced the preferential production of Th1 cytokines (interferon γ/granulocyte macrophage colony-stimulating factor) while G28z preferentially induced Th2 cytokines (interleukin-4/interleukin-10). Inclusion of 4-1BB in G28BBz could only partially ameliorate the Th2-polarizing effect of CD28. 4-1BB induced superior expansion of CAR T cells in vitro and in vivo. T cells expressing GPC3-CARs incorporating CD28, 4-1BB, or both induced sustained tumor regressions in two xenogeneic tumor models. Thus, GBBz CAR endows T cells with superior proliferative potential, potent antitumor activity, and a Th1-biased cytokine profile, justifying further clinical development of GBBz CAR for immunotherapy of GPC3-positive solid tumors.
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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.