{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:12:13Z","timestamp":1791295933167,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,1,3]],"date-time":"2013-01-03T00:00:00Z","timestamp":1357171200000},"content-version":"vor","delay-in-days":2,"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>Since the first report in 1976, accumulated clinical evidence has supported intravesical <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>acillus <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>almette\u2013<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>uerin (<jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content>) therapy as one of the standard methods of management of intermediate\u2010 and high\u2010risk non\u2010muscle invasive bladder cancer. Despite its efficacy, intravesical <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> therapy is associated with a variety of adverse events (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s), most of which are tolerable or controllable with supportive care. However, some patients receiving intravesical <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> therapy may experience uncommon but severe <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s, leading to cessation of <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> therapy. Not all, but most severe <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s result from either local or systemic infection with live <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content>. Intravesical instillation of <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> elicits multiple immune reactions, although the precise immunological mechanism of <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> therapy is not clear. It is convenient to separate the complex reactions into the following three categories: infection of urothelial cells or bladder cancer cells, induction of immune reactions, and induction of antitumor effects. Recently, our knowledge about each category has increased. Based on this understanding, predictors of the efficacy of intravesical <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> therapy, such as urinary cytokine measurement and cytokine gene polymorphism, have been investigated. Recently, preclinical studies using a novel engineered mycobacterium vaccine have been conducted to overcome the limitations of <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> therapy. One approach is <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>h1 cytokine\u2010expressing recombinant forms of <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content>; another approach is development of non\u2010live bacterial agents to avoid <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s due to live <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> infection. We also briefly describe our approach using an octaarginine\u2010modified liposome\u2010incorporating <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> cell wall component to develop future substitutes for live <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content>. (<jats:italic>Cancer Sci<\/jats:italic> 2013; 104: 22\u201327)<\/jats:p>","DOI":"10.1111\/cas.12075","type":"journal-article","created":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T15:39:31Z","timestamp":1353944371000},"page":"22-27","source":"Crossref","is-referenced-by-count":160,"title":["<scp>B<\/scp>acillus <scp>C<\/scp>almette\u2013<scp>G<\/scp>uerin (<scp>BCG<\/scp>) immunotherapy for bladder cancer: Current understanding and perspectives on engineered <scp>BCG<\/scp> vaccine"],"prefix":"10.1111","volume":"104","author":[{"given":"Koji","family":"Kawai","sequence":"first","affiliation":[{"name":"Department of Urology Faculty of Medicine University of Tsukuba Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Urology Faculty of Medicine University of Tsukuba Tokyo 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