ArticleScientific reports2016
Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
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- Generation of a Human-Mouse Chimeric Anti-Japanese Encephalitis Virus and Zika Virus Monoclonal Antibody Using CDR Grafting.Microorganisms · 2025Article
- High-plex imaging of hepatoblastoma and adjacent liver in pediatric patients reveals a predominant myeloid infiltrate expressing immune-checkpoints.Cancer immunology, immunotherapy : CII · 2025Article
- Review
- Targeting CD44 Variant 5 with an Antibody-Drug Conjugate Is an Effective Therapeutic Strategy for Intrahepatic Cholangiocarcinoma.Cancer research · 2023Article
- Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients.International journal of molecular sciences · 2023Article
- The IgG4 hinge with CD28 transmembrane domain improves VNature communications · 2023Article
- Derivation and Preclinical Characterization of CYT-303, a Novel NKp46-NK Cell Engager Targeting GPC3.Cells · 2023Article
- Conversion of primary liver cancer after targeted therapy for liver cancer combined with AFP-targeted CAR T-cell therapy: a case report.Frontiers in immunology · 2023Article
- Humanization of the Shark VCurrent protocols · 2023Article
- 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
- Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- A universal in silico V(D)J recombination strategy for developing humanized monoclonal antibodies.Journal of nanobiotechnology · 2022Article
- Combination Therapy of Hepatocellular Carcinoma by GPC3-Targeted Bispecific Antibody and Irinotecan is Potent in Suppressing Tumor Growth in Mice.Molecular cancer therapeutics · 2022Article
- Highly Potent Immunotoxins Targeting the Membrane-distal N-lobe of GPC3 for Immunotherapy of Hepatocellular Carcinoma.Journal of Cancer · 2022Article
- DT389-YP7, a Recombinant Immunotoxin against Glypican-3 That Inhibits Hepatocellular Cancer Cells: An In Vitro Study.Toxins · 2021Article
- Review
- CAR T cells targeting tumor-associated exons of glypican 2 regress neuroblastoma in mice.Cell reports. Medicine · 2021Article
- Generation of fully human anti-GPC3 antibodies with high-affinity recognition of GPC3 positive tumors.Investigational new drugs · 2021Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell-mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer.
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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.