{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:01:08Z","timestamp":1793041268593,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,3,4]],"date-time":"2011-03-04T00:00:00Z","timestamp":1299196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:p>Glypican\u20103 (GPC3) is an onco\u2010fetal antigen that is overexpressed in human hepatocellular carcinoma (HCC), and is only expressed in the placenta and embryonic liver among normal tissues. Previously, we identified an HLA\u2010A2\u2010restricted GPC3<jats:sub>144\u2013152<\/jats:sub> (FVGEFFTDV) peptide that can induce GPC3\u2010reactive CTLs without inducing autoimmunity in HLA\u2010A2 transgenic mice. In this study, we carried out a phase I clinical trial of HLA\u2010A2\u2010restricted GPC3<jats:sub>144\u2013152<\/jats:sub> peptide vaccine in 14 patients with advanced HCC. Immunological responses were analyzed by <jats:italic>ex vivo<\/jats:italic>\u03b3\u2010interferon enzyme\u2010linked immunospot assay. The frequency of GPC3<jats:sub>144\u2013152<\/jats:sub> peptide\u2010specific CTLs after vaccination (mean, 96; range, 5\u2013441) was significantly larger than that before vaccination (mean, 6.5; range, 0\u201343) (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01). An increase in the GPC3<jats:sub>144\u2013152<\/jats:sub> peptide\u2010specific CTL frequency was observed in 12 (86%) of 14 patients after vaccination. Additionally, there was a significant correlation between the maximum value of GPC3<jats:sub>144\u2013152<\/jats:sub> peptide\u2010specific CTLs after vaccination and the dose of the peptide injected (<jats:italic>P<\/jats:italic>\u2003=\u20030.0166, <jats:italic>r<\/jats:italic>\u2003=\u20030.665). Moreover, we established several GPC3<jats:sub>144\u2013152<\/jats:sub> peptide\u2010specific CTL clones from PBMCs of patients vaccinated with GPC3<jats:sub>144\u2013152<\/jats:sub> peptide by single cell sorting using Dextramer and CD107a antibody. These CTL clones had high avidity (the recognition efficiency showing 50% cytotoxicity was 10<jats:sup>\u221210<\/jats:sup> or 10<jats:sup>\u221211<\/jats:sup>\u2003M) and could recognize HCC cell lines expressing GPC3 in an HLA\u2010class I\u2010restricted manner. These results suggest that GPC3<jats:sub>144\u2013152<\/jats:sub> peptide vaccine can induce high avidity CTLs capable of killing HCC cells expressing GPC3. This trial was registered with University Hospital Medical Information Network number 000001395. (<jats:italic>Cancer Sci<\/jats:italic> 2011; 102: 918\u2013925)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2011.01896.x","type":"journal-article","created":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T05:11:27Z","timestamp":1296537087000},"page":"918-925","source":"Crossref","is-referenced-by-count":66,"title":["HLA\u2010A2\u2010restricted glypican\u20103 peptide\u2010specific CTL clones induced by peptide vaccine show high avidity and antigen\u2010specific killing activity against tumor 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