Adenovirus-mediated interleukin-18 mutant in vivo gene transfer inhibits tumor growth through the induction of T cell immunity and activation of natural killer cell cytotoxicity

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dc.contributor.authorKyung Sun Hwang-
dc.contributor.authorWon-Kyung Cho-
dc.contributor.authorJin Sang Yoo-
dc.contributor.authorY R Seong-
dc.contributor.authorB K Kim-
dc.contributor.authorS Y Kim-
dc.contributor.authorDong Soo Im-
dc.date.accessioned2017-04-19T09:01:25Z-
dc.date.available2017-04-19T09:01:25Z-
dc.date.issued2004-
dc.identifier.issn09291903-
dc.identifier.uri10.1038/sj.cgt.7700711ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/6614-
dc.description.abstractWe report here that gene transfer using recombinant adenoviruses encoding interleukin (IL)-18 mutants induces potent antitumor activity in vivo. The precursor form of IL-18 (ProIL-18) is processed by caspase-1 to produce bioactive IL-18, but its cleavage by caspase-3 (CPP32) produces an inactive form. To prepare IL-18 molecules with an effective antitumor activity, a murine IL-18 mutant with the signal sequence of murine granulocyte-macrophage (GM)- colony stimulating factor (CSF) at the 5′-end of mature IL-18 cDNA (GMmIL-18) and human IL-18 mutant with the prepro leader sequence of trypsin (PPT), which is not cleaved by caspase-3 (PPThIL-18CPP32-), respectively, were constructed. Adenovirus vectors carrying GMmIL-18 or PPThIL-18CPP32- produced bioactive IL-18. Ad.GMmIL-18 had a more potent antitumor effect than Ad.mProIL-18 encoding immature IL-18 in renal cell adenocarcinoma (Renca) tumor-bearing mice. Tumor-specific cytotoxic T lymphocytes, the induction of Th1 cytokines, and an augmented natural killer (NK) cell activity were detected in Renca tumor-bearing mice treated with Ad.GMmIL-18. An immunohistological analysis revealed that CD4+ and CD8+ T cells abundantly infiltrated into tumors of mice treated with Ad.GMmIL-18. Huh-7 human hepatoma tumor growth in nude mice with a defect of T cell function was significantly inhibited by Ad.PPThIL-18CPP32- compared with Ad.hProIL-18 encoding immature IL-18. Nude mice treated with Ad.PPThIL-18CPP32- contained NK cells with increased cytotoxicity. The results suggest that the release of mature IL-18 in tumors is required for achieving an antitumor effect including tumor-specific cellular immunity and augmented NK cell-mediated cytotoxicity. These optimally designed IL-18 mutants could be useful for improving the antitumor effectiveness of wild-type IL-18.-
dc.publisherSpringer-Nature Pub Group-
dc.titleAdenovirus-mediated interleukin-18 mutant in vivo gene transfer inhibits tumor growth through the induction of T cell immunity and activation of natural killer cell cytotoxicity-
dc.title.alternativeAdenovirus-mediated interleukin-18 mutant in vivo gene transfer inhibits tumor growth through the induction of T cell immunity and activation of natural killer cell cytotoxicity-
dc.typeArticle-
dc.citation.titleCancer Gene Therapy-
dc.citation.number6-
dc.citation.endPage407-
dc.citation.startPage397-
dc.citation.volume11-
dc.contributor.alternativeName황경선-
dc.contributor.alternativeName조원경-
dc.contributor.alternativeName유진상-
dc.contributor.alternativeName성영림-
dc.contributor.alternativeName김범경-
dc.contributor.alternativeName김삼용-
dc.contributor.alternativeName임동수-
dc.identifier.bibliographicCitationCancer Gene Therapy, vol. 11, no. 6, pp. 397-407-
dc.identifier.doi10.1038/sj.cgt.7700711-
dc.subject.keywordAdenovirus vector-
dc.subject.keywordIL-18 mutant-
dc.subject.keywordLiver cancer-
dc.subject.keywordRenal cancer-
dc.subject.localAdenovirus vector-
dc.subject.localIL-18 mutant-
dc.subject.localLiver cancer-
dc.subject.localRenal cancer-
dc.description.journalClassY-
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