ArticleOncotarget2017
Construction of an immunotoxin, HN3-mPE24, targeting glypican-3 for liver cancer therapy.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Glypican-3-targeted therapy in hepatocellular carcinoma: biological insights and therapeutic strategies.Cancer gene therapy · 2026Review
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
- Organ-specific delivery of an mRNA-encoded bispecific T cell engager targeting glypican-3 in hepatocellular carcinoma.Nature communications · 2025Article
- A new treatment for canine B-cell lymphoma based on a recombinant single-domain antibody immunotoxin derived fromFrontiers in veterinary science · 2025Article
- Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023Review
- A New Combination: Anti Glypican-3 scFv and Diphtheria Toxin with the Best Flexible Linker.The protein journal · 2022Article
- Novel Nanotechnology Approaches to Overcome Drug Resistance in the Treatment of Hepatocellular Carcinoma: Glypican 3 as a Useful Target for Innovative Therapies.International journal of molecular sciences · 2022Review
- Review
- GPC1-Targeted Immunotoxins Inhibit Pancreatic Tumor Growth in Mice via Depletion of Short-lived GPC1 and Downregulation of Wnt Signaling.Molecular cancer therapeutics · 2022Article
- Highly Potent Immunotoxins Targeting the Membrane-distal N-lobe of GPC3 for Immunotherapy of Hepatocellular Carcinoma.Journal of Cancer · 2022Article
- Article
- Glypican-3: A Novel and Promising Target for the Treatment of Hepatocellular Carcinoma.Frontiers in oncology · 2022Review
- ADP-ribosyl transferase activity and gamma radiation cytotoxicity of Pseudomonas aeruginosa exotoxin A.AMB Express · 2021Article
- Immunotoxins: From Design to Clinical Application.Biomolecules · 2021Article
- DT389-YP7, a Recombinant Immunotoxin against Glypican-3 That Inhibits Hepatocellular Cancer Cells: An In Vitro Study.Toxins · 2021Article
- Review
- A GPC2 antibody-drug conjugate is efficacious against neuroblastoma and small-cell lung cancer via binding a conformational epitope.Cell reports. Medicine · 2021Article
- Recombinant immunotoxin targeting GPC3 is cytotoxic to H446 small cell lung cancer cells.Oncology letters · 2021Article
- The Role of Glypicans in Cancer Progression and Therapy.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Glypican-3: A molecular marker for the detection and treatment of hepatocellular carcinomaLiver research (Beijing, China) · 2020Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Glypican-3 (GPC3) is overexpressed in hepatocellular carcinoma (HCC). We constructed a recombinant immunotoxin, HN3-mPE24, which contains a truncated form of Pseudomonas exotoxin A. The toxin portion lacks most of domain II and has seven point mutations in domain III to remove the B-cell epitopes thought to be responsible for causing off-target side effects and immunogenicity. We also fused a bivalent HN3 to mPE24. We tested these two molecules for GPC3 binding and cytotoxicity in HCC cell models. The KD values of HN3-mPE24 and HN3-HN3-mPE24 for GPC3-expressing tumor cells were 12 nM and 1.4 nM, respectively. The IC50 values of HN3-mPE24 and HN3-HN3-mPE24 for HCC cells were 0.2 nM and 0.4 nM, respectively. We also evaluated their toxicity and anti-tumor efficacy in mice. The maximum tolerated doses of HN3-mPE24 and HN3-HN3-mPE24 were 7 mg kg-1 and 3.6 mg kg-1, respectively. We treated mice with 5 mg kg-1 of HN3-mPE24 intravenously every other day for ten injections. The alpha-fetoprotein level of HN3-mPE24 treated group was approximately 700 fold less than that of the untreated group (1.1 μg ml-1 vs. 692.1 μg ml-1). In addition, 25% of the mice treated with HN3-mPE24 survived to the end of this study, which was 105 days after HCC tumor implantation. In conclusion, the HN3-mPE24 immunotoxin caused liver tumor regressions and extended survival with no significant side effects in mice. It is a promising candidate for the treatment of liver cancer that may be readily translated to humans.
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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.