{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:38:53Z","timestamp":1791999533223,"version":"4.4.0"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"DOI":"10.3389\/fonc.2019.00248","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T09:12:17Z","timestamp":1554887537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":116,"title":["Next-Generation Cancer Immunotherapy Targeting Glypican-3"],"prefix":"10.3389","volume":"9","author":[{"given":"Yasuhiro","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itaru","family":"Endo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Nakatsura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3389\/fonc.2014.00385","article-title":"CTLA-4 and PD-1 pathway blockade: combinations in the clinic","volume":"4","author":"Callahan","year":"2015","journal-title":"Front Oncol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1056\/NEJMoa1305133","article-title":"Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma","volume":"369","author":"Hamid","year":"2013","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nri1842","article-title":"Adoptive immunotherapy for cancer: building on success","volume":"6","author":"Gattinoni","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1056\/NEJMoa1407222","article-title":"Chimeric antigen receptor T cells for sustained remissions in leukemia","volume":"371","author":"Maude","year":"2014","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nature22991","article-title":"An immunogenic personal neoantigen vaccine for patients with melanoma","volume":"547","author":"Ott","year":"2017","journal-title":"Nature."},{"key":"B6","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nature23003","article-title":"Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer","volume":"547","author":"Sahin","year":"2017","journal-title":"Nature."},{"key":"B7","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41586-018-0792-9","article-title":"Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial","volume":"565","author":"Keskin","year":"2019","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1411087","article-title":"PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma","volume":"372","author":"Ansell","year":"2015","journal-title":"N Eng J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature21349","article-title":"Elements of cancer immunity and the cancer\u2013immune set point","volume":"541","author":"Chen","year":"2017","journal-title":"Nature."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1038\/nm1622","article-title":"Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy","volume":"13","author":"Apetoh","year":"2007","journal-title":"Nat Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.3389\/fimmu.2017.01679","article-title":"Neoantigens generated by individual mutations and their role in cancer immunity and immunotherapy","volume":"8","author":"Efremova","year":"2017","journal-title":"Front Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.clcc.2016.07.007","article-title":"The potential value of immunotherapy in colorectal cancers: review of the evidence for programmed death-1 inhibitor therapy","volume":"15","author":"Toh","year":"2016","journal-title":"Clin Colorectal Cancer."},{"key":"B13","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1093\/intimm\/dxw022","article-title":"T-cell adoptive immunotherapy using tumor-infiltrating T cells and genetically engineered TCR-T cells","volume":"28","author":"Ikeda","year":"2016","journal-title":"Int Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/S0006-291X(03)00908-2","article-title":"Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker","volume":"306","author":"Nakatsura","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"B15","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1172\/JCI200113712","article-title":"Glypicans: proteoglycans with a surprise","volume":"108","author":"Filmus","year":"2001","journal-title":"J Clin Invest"},{"key":"B16","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/ng0396-241","article-title":"Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome","volume":"12","author":"Pilia","year":"1996","journal-title":"Nat Gen."},{"key":"B17","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.1158\/0008-5472.CAN-04-4244","article-title":"Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling","volume":"65","author":"Capurro","year":"2005","journal-title":"Cancer Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1128\/MCB.01164-09","article-title":"A novel mechanism of sequestering fibroblast growth factor 2 by glypican in lipid rafts, allowing skeletal muscle differentiation","volume":"30","author":"Guti\u00e9rrez","year":"2010","journal-title":"Mol Cell Biol."},{"key":"B19","first-page":"255","article-title":"Glypican-3-deficient mice exhibit the overgrowth and renal abnormalities typical of the Simpson\u2013Golabi\u2013Behmel syndrome","volume":"146","author":"Cano-Gauci","year":"1999","journal-title":"J Cell Biol"},{"key":"B20","first-page":"807","article-title":"Frequent silencing of the GPC3 gene in ovarian cancer cell lines","volume":"59","author":"Lin","year":"1999","journal-title":"Cancer Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"71","DOI":"10.2165\/00063030-200519020-00001","article-title":"Usefulness of the novel oncofetal antigen glypican-3 for diagnosis of hepatocellular carcinoma and melanoma","volume":"19","author":"Nakatsura","year":"2005","journal-title":"BioDrugs."},{"key":"B22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/S0016-5085(03)00689-9","article-title":"Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma","volume":"125","author":"Capurro","year":"2003","journal-title":"Gastroenterology."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1111\/j.1349-7006.2009.01206.x","article-title":"Glypican-3 expression is correlated with poor prognosis in hepatocellular carcinoma","volume":"100","author":"Shirakawa","year":"2009","journal-title":"Cancer Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1002\/j.1460-2075.1994.tb06438.x","article-title":"Release of GPI-anchored membrane proteins by a cell-associated GPI-specific phospholipase D","volume":"13","author":"Metz","year":"1994","journal-title":"EMBO J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1042\/BJ20070511","article-title":"Mammalian Notum induces the release of glypicans and other GPI-anchored proteins from the cell surface","volume":"410","author":"Traister","year":"2008","journal-title":"Biochem J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nature14259","article-title":"Notum deacylates Wnt proteins to suppress signaling activity","volume":"519","author":"Kakugawa","year":"2015","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.1158\/0008-5472.CAN-03-2191","article-title":"Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma","volume":"64","author":"Hippo","year":"2004","journal-title":"Cancer Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"8630","DOI":"10.1158\/1078-0432.CCR-04-1177","article-title":"Mouse homolog of a novel human oncofetal antigen, glypican-3, evokes T-cell-mediated tumor rejection without autoimmune reactions in mice","volume":"10","author":"Nakatsura","year":"2004","journal-title":"Clin Cancer Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1158\/1078-0432.CCR-05-2267","article-title":"Identification of HLA-A2- or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma","volume":"12","author":"Komori","year":"2006","journal-title":"Clin Cancer Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3686","DOI":"10.1158\/1078-0432.CCR-11-3044","article-title":"Phase I trial of a glypican-3-derived peptide vaccine for advanced hepatocellular carcinoma: immunologic evidence and potential for improving overall survival","volume":"18","author":"Sawada","year":"2012","journal-title":"Clin Cancer Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1129483","DOI":"10.1080\/2162402X.2015.1129483","article-title":"Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients","volume":"5","author":"Sawada","year":"2016","journal-title":"Oncoimmunology."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e1238542","DOI":"10.1080\/2162402X.2016.1238542","article-title":"Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma","volume":"5","author":"Suzuki","year":"2016","journal-title":"Oncoimmunology."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e1377872","DOI":"10.1080\/2162402X.2017.1377872","article-title":"Phase I study of glypican-3-derived peptide vaccine therapy for patients with refractory pediatric solid tumors","volume":"7","author":"Tsuchiya","year":"2017","journal-title":"Oncoimmunology."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e1346764","DOI":"10.1080\/2162402X.2017.1346764","article-title":"Immunological efficacy of glypican-3 peptide vaccine in patients with advanced hepatocellular carcinoma","volume":"6","author":"Tsuchiya","year":"2017","journal-title":"Oncoimmunology."},{"key":"B35","doi-asserted-by":"publisher","first-page":"985","DOI":"10.3892\/ijo.32.5.985","article-title":"HLA-A2 and -A24-restricted glypican-3-derived peptide vaccine induces specific CTLs: preclinical study using mice","volume":"32","author":"Motomura","year":"2008","journal-title":"Int J Oncol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1158\/1078-0432.CCR-12-2616","article-title":"First-in-man phase I study of GC33, a novel recombinant humanized antibody against glypican-3, in patients with advanced hepatocellular carcinoma","volume":"19","author":"Zhu","year":"2013","journal-title":"Clin Cancer Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/cas.12368","article-title":"Japanese phase I study of GC33, a humanized antibody against glypican-3 for advanced hepatocellular carcinoma","volume":"105","author":"Ikeda","year":"2014","journal-title":"Cancer Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1111\/j.1349-7006.2011.01896.x","article-title":"HLA-A2-restricted glypican-3 peptide-specific CTL clones induced by peptide vaccine show high avidity and antigen-specific killing activity against tumor cells","volume":"102","author":"Yoshikawa","year":"2011","journal-title":"Cancer Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.4161\/hv.24179","article-title":"Remarkable tumor lysis in a hepatocellular carcinoma patient immediately following glypican-3-derived peptide vaccination: an autopsy case","volume":"9","author":"Sawada","year":"2013","journal-title":"Hum Vaccin Immunother"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e1062209","DOI":"10.1080\/2162402X.2015.1062209","article-title":"Identification of glypican-3-derived long peptides activating both CD8\u00b1 and CD4\u00b1 T cells; prolonged overall survival in cancer patients with Th cell response","volume":"5","author":"Sayem","year":"2016","journal-title":"Oncoimmunology."},{"key":"B41","doi-asserted-by":"publisher","first-page":"338","DOI":"10.4161\/hv.27217","article-title":"Significant clinical response of progressive recurrent ovarian clear cell carcinoma to glypican-3-derived peptide vaccine therapy: two case reports","volume":"10","author":"Suzuki","year":"2014","journal-title":"Hum Vaccin Immunother"},{"key":"B42","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/S1357-4310(99)01451-3","article-title":"HLA class I antigen downregulation in human cancers: T-cell immunotherapy revives an old story","volume":"5","author":"Hicklin","year":"1999","journal-title":"Mol Med Today."},{"key":"B43","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1038\/ni1102-999","article-title":"Natural selection of tumor variants in the generation of \u201ctumor escape\u201d phenotypes","volume":"3","author":"Khong","year":"2002","journal-title":"Nat Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.4161\/hv.23990","article-title":"Peptide intra-tumor injection for cancer immunotherapy: enhancement of tumor cell antigenicity is a novel and attractive strategy","volume":"9","author":"Nobuoka","year":"2013","journal-title":"Hum Vaccin Immunother"},{"key":"B45","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s00262-012-1366-6","article-title":"Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy","volume":"62","author":"Nobuoka","year":"2013","journal-title":"Cancer Immunol Immunother"},{"key":"B46","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3892\/ijo.2014.2737","article-title":"Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes","volume":"46","author":"Sawada","year":"2015","journal-title":"Int J Oncol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.bbrep.2016.02.010","article-title":"Enhancement of antitumor effect by peptide vaccine therapy in combination with anti-CD4 antibody: Study in a murine model","volume":"5","author":"Fujinami","year":"2016","journal-title":"Biochem Biophys Rep"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.3892\/ijo.2013.2044","article-title":"Analysis of cytotoxic T lymphocytes from a patient with hepatocellular carcinoma who showed a clinical response to vaccination with a glypican 3 derived peptide","volume":"43","author":"Tada","year":"2013","journal-title":"Int J Oncol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"9832","DOI":"10.1158\/0008-5472.CAN-08-1973","article-title":"Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer","volume":"68","author":"Ishiguro","year":"2008","journal-title":"Cancer Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"eaal4291","DOI":"10.1126\/scitranslmed.aal4291","article-title":"An anti-glypican 3\/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors","volume":"9","author":"Ishiguro","year":"2017","journal-title":"Sci Transl Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene xiloleucel CAR T-cell therapy in refractory large B-cell lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"New Eng J Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"eaaa0984","DOI":"10.1126\/scitranslmed.aaa0984","article-title":"A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma","volume":"9","author":"O'rourke","year":"2017","journal-title":"Sci Trans Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1053\/j.gastro.2018.03.029","article-title":"Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial","volume":"155","author":"Beatty","year":"2018","journal-title":"Gastroenterology."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1002\/pros.23214","article-title":"Phase I trial of anti-PSMA designer CAR-T cells in prostate cancer: possible role for interacting interleukin 2-T cell pharmacodynamics as a determinant of clinical response","volume":"76","author":"Junghans","year":"2016","journal-title":"Prostate."},{"key":"B56","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.ymthe.2017.10.019","article-title":"CAR-T cells: a systematic review and mixed methods analysis of the clinical trial landscape","volume":"26","author":"Pettitt","year":"2018","journal-title":"Mol Ther."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science."},{"key":"B58","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/nbt.4086","article-title":"IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor","volume":"36","author":"Adachi","year":"2018","journal-title":"Nat Biotechnol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"690","DOI":"10.3389\/fimmu.2016.00690","article-title":"Anti-GPC3-CAR T cells suppress the growth of tumor cells in patient-derived xenografts of hepatocellular carcinoma","volume":"7","author":"Jiang","year":"2017","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1089\/hum.2016.025","article-title":"Redirecting T cells to glypican-3 with 4-1BB zeta chimeric antigen receptors results in Th1 polarization and potent antitumor activity","volume":"28","author":"Li","year":"2017","journal-title":"Hum Gene Ther."},{"key":"B61","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.stem.2018.10.005","article-title":"Enhancing T cell receptor stability in rejuvenated iPSC-derived T cells improves their use in cancer immunotherapy","volume":"6","author":"Minagawa","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1038\/modpathol.3800436","article-title":"The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma","volume":"18","author":"Yamauchi","year":"2005","journal-title":"Mod Pathol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.cca.2013.04.026","article-title":"Reevaluation of glypican-3 as a serological marker for hepatocellular carcinoma","volume":"423","author":"Chen","year":"2013","journal-title":"Clin Chim Acta."},{"key":"B64","doi-asserted-by":"publisher","first-page":"37835","DOI":"10.18632\/oncotarget.14271","article-title":"Perioperative plasma glypican-3 level may enable prediction of the risk of recurrence after surgery in patients with stage I hepatocellular carcinoma","volume":"8","author":"Ofuji","year":"2017","journal-title":"Oncotarget."},{"key":"B65","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/cas.13485","article-title":"Cancer immunotherapy-targeted glypican-3 or neoantigens","volume":"109","author":"Shimizu","year":"2018","journal-title":"Cancer Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1126\/science.1840703","article-title":"A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma","volume":"254","author":"Van der Bruggen","year":"1991","journal-title":"Science."}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2019.00248\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T09:12:19Z","timestamp":1554887539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2019.00248\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,10]]},"references-count":66,"alternative-id":["10.3389\/fonc.2019.00248"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2019.00248","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,10]]},"article-number":"248"}}