{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T19:01:11Z","timestamp":1775588471120,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T00:00:00Z","timestamp":1352332800000},"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":[[2013,1]]},"abstract":"<jats:p><jats:styled-content style=\"fixed-case\">OTS<\/jats:styled-content>11101 is a novel peptide vaccine that acts as an angiogenesis inhibitor by inducing cytotoxic <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> lymphocyte (<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content>) cells that specifically target vascular endothelial cells expressing vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>) receptor 1. We conducted a phase <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content> study to evaluate the safety, tolerability, maximum tolerated dose, and pharmacodynamic biomarker status of this vaccine. Nine patients with advanced solid tumors received 1.0, 2.0, or 3.0\u00a0mg of <jats:styled-content style=\"fixed-case\">OTS<\/jats:styled-content>11101 subcutaneously, once a week in a 28\u2010day cycle. Three patients experienced grade 1 injection site reactions, which were the most frequent adverse events. Grade 2 proteinuria and hypertension each occurred in one patient. As other toxicities were generally mild, the maximum tolerated dose was not reached. Furthermore, we explored the induction of specific activated <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content>s, and biomarkers related to angiogenesis. A pharmacodynamics study revealed that induction of specific <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content>s was observed for a dose of 2.0 and 3.0\u00a0mg. The serum concentrations of soluble <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> receptor 1 and 2 after vaccination increased significantly compared with baseline. A microarray was performed to give a comprehensive analysis of gene expression, suggesting that <jats:styled-content style=\"fixed-case\">OTS<\/jats:styled-content>11101 vaccination resulted in <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cell activation in a clinical setting. In conclusion, <jats:styled-content style=\"fixed-case\">OTS<\/jats:styled-content>11101 was well tolerated in patients up to 3.0\u00a0mg once weekly and our biomarker analysis suggested that this anti\u2010angiogenesis vaccine is biologically active. (<jats:italic>Cancer Sci<\/jats:italic> 2013; 104: 98\u2013104)<\/jats:p>","DOI":"10.1111\/cas.12034","type":"journal-article","created":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T05:39:56Z","timestamp":1349069996000},"page":"98-104","source":"Crossref","is-referenced-by-count":14,"title":["Phase <scp>I<\/scp> trial of <scp>OTS<\/scp>11101, an anti\u2010angiogenic vaccine targeting vascular endothelial growth factor receptor 1 in solid tumor"],"prefix":"10.1111","volume":"104","author":[{"given":"Hidetoshi","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Kinki University Faculty of Medicine Osaka\u2010Sayama Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayasu","family":"Kurata","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Kinki University Faculty of Medicine Osaka\u2010Sayama Osaka 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