Llovet JM, Kelley RK, Villanueva A et al (2021) Hepatocellular carcinoma. Nat Rev Dis Primers 7:6. https://doi.org/10.1038/s41572-020-00240-3

Article  PubMed  Google Scholar 

Villanueva A (2019) Hepatocellular Carcinoma. New England J Med 380:1450–1462. https://doi.org/10.1056/NEJMra1713263

Article  CAS  Google Scholar 

Finn RS, Qin S, Ikeda M et al (2020) Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. New England J Med 382:1894–1905. https://doi.org/10.1056/NEJMoa1915745

Article  CAS  Google Scholar 

Yang X, Wang D, Lin J et al (2020) Atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. Lancet Oncol 21:e412. https://doi.org/10.1016/S1470-2045(20)30430-7

Article  PubMed  Google Scholar 

Ho M, Kim H (2011) Glypican-3: a new target for cancer immunotherapy. Eur J Cancer 47:333–338. https://doi.org/10.1016/j.ejca.2010.10.024

Article  CAS  PubMed  Google Scholar 

De Cat B, David G (2001) Developmental roles of the glypicans. Semin Cell Dev Biol 12:117–125

Article  PubMed  Google Scholar 

Baumhoer D, Tornillo L, Stadlmann S et al (2008) Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples. Am J Clin Pathol 129:899–906. https://doi.org/10.1309/HCQWPWD50XHD2DW6

Article  PubMed  Google Scholar 

Capurro MI, Xiang Y-Y, Lobe C et al (2005) Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling. Cancer Res 65:6245–6254

Article  CAS  PubMed  Google Scholar 

Capurro MI, Xu P, Shi W et al (2008) Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding. Dev Cell 14:700–711. https://doi.org/10.1016/j.devcel.2008.03.006

Article  CAS  PubMed  Google Scholar 

Lai JP, Sandhu DS, Yu C et al (2008) Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma. Hepatology 47:1211–1222. https://doi.org/10.1002/hep.22202

Article  CAS  PubMed  Google Scholar 

Zhao Z, Cui T, Wei F et al (2024) Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target. Front Oncol 14:1367364. https://doi.org/10.3389/fonc.2024.1367364

Article  CAS  PubMed  PubMed Central  Google Scholar 

Capurro M, Martin T, Shi W et al (2014) Glypican-3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling. J Cell Sci 127:1565–1575. https://doi.org/10.1242/jcs.140871

Article  CAS  PubMed  Google Scholar 

Zhou F, Shang W, Yu X et al (2018) Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment. Med Res Rev 38:741–767. https://doi.org/10.1002/med.21455

Article  CAS  PubMed  Google Scholar 

Sun H, Xing C, Jiang S et al (2022) Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report. Front Immunol 13:963031. https://doi.org/10.3389/fimmu.2022.963031

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi Y, Shi D, Chi J et al (2023) Combined local therapy and CAR-GPC3 T-cell therapy in advanced hepatocellular carcinoma: a proof-of-concept treatment strategy. Cancer Commun (Lond) 43:1064–1068. https://doi.org/10.1002/cac2.12472

Article  PubMed  Google Scholar 

Ishiguro T, Sugimoto M, Kinoshita Y et al (2008) Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. Cancer Res 68:9832–9838. https://doi.org/10.1158/0008-5472.Can-08-1973

Article  CAS  PubMed  Google Scholar 

Zhu AX, Gold PJ, El-Khoueiry AB et al (2013) First-in-man phase I study of GC33, a novel recombinant humanized antibody against glypican-3, in patients with advanced hepatocellular carcinoma. Clin Cancer Res 19:920–928. https://doi.org/10.1158/1078-0432.CCR-12-2616

Article  CAS  PubMed  Google Scholar 

Ikeda M, Ohkawa S, Okusaka T et al (2014) Japanese phase I study of GC33, a humanized antibody against glypican-3 for advanced hepatocellular carcinoma. Cancer Sci 105:455–462. https://doi.org/10.1111/cas.12368

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fu Y, Urban DJ, Nani RR et al (2019) Glypican-3-Specific Antibody Drug Conjugates Targeting Hepatocellular Carcinoma. Hepatology 70:563–576. https://doi.org/10.1002/hep.30326

Article  CAS  PubMed  Google Scholar 

Fleming BD, Urban DJ, Hall MD et al (2020) Engineered Anti-GPC3 Immunotoxin, HN3-ABD-T20, Produces Regression in Mouse Liver Cancer Xenografts Through Prolonged Serum Retention. Hepatology 71:1696–1711. https://doi.org/10.1002/hep.30949

Article  CAS  PubMed  Google Scholar 

Labrijn AF, Janmaat ML, Reichert JM et al (2019) Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov 18:585–608. https://doi.org/10.1038/s41573-019-0028-1

Article  CAS  PubMed  Google Scholar 

Grandjenette C, Dicato M, Diederich M (2015) Bispecific antibodies: an innovative arsenal to hunt, grab and destroy cancer cells. Curr Pharm Biotechnol 16:670–683

Article  CAS  PubMed  Google Scholar 

Surowka M, Klein C (2024) A pivotal decade for bispecific antibodies? MAbs 16:2321635. https://doi.org/10.1080/19420862.2024.2321635

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ishiguro T, Sano Y, Komatsu S-I, et al (2017) An anti-glypican 3/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors. Sci Transl Med 9 https://doi.org/10.1126/scitranslmed.aal4291.

Komatsu S-I, Kayukawa Y, Miyazaki Y et al (2022) Determination of starting dose of the T cell-redirecting bispecific antibody ERY974 targeting glypican-3 in first-in-human clinical trial. Sci Rep 12:12312. https://doi.org/10.1038/s41598-022-16564-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee H-H, Wang Y-N, Xia W et al (2019) Removal of N-Linked Glycosylation Enhances PD-L1 Detection and Predicts Anti-PD-1/PD-L1 Therapeutic Efficacy. Cancer Cell 36 https://doi.org/10.1016/j.ccell.2019.06.008.

Hippo Y, Watanabe K, Watanabe A et al (2004) Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res 64:2418–2423

Article  CAS  PubMed  Google Scholar 

Montalbano M, Rastellini C, McGuire JT et al (2018) Role of Glypican-3 in the growth, migration and invasion of primary hepatocytes isolated from patients with hepatocellular carcinoma. Cell Oncol (Dordr) 41:169–184. https://doi.org/10.1007/s13402-017-0364-2

Article  CAS  PubMed  Google Scholar 

Li N, Wei L, Liu X et al (2019) A Frizzled-Like Cysteine-Rich Domain in Glypican-3 Mediates Wnt Binding and Regulates Hepatocellular Carcinoma Tumor Growth in Mice. Hepatology 70:1231–1245. https://doi.org/10.1002/hep.30646

Article  CAS  PubMed  Google Scholar 

Li J, Xiang L, Wang Q et al (2022) Highly Potent Immunotoxins Targeting the Membrane-distal N-lobe of GPC3 for Immunotherapy of Hepatocellular Carcinoma. J Cancer 13:1370–1384. https://doi.org/10.7150/jca.66978

Article  CAS  PubMed  PubMed Central  Google Scholar 

Surowka M, Schaefer W, Klein C (2021) Ten years in the making: application of CrossMab technology for the development of therapeutic bispecific antibodies and antibody fusion proteins. MAbs 13:1967714. https://doi.org/10.1080/19420862.2021.1967714