DC Field | Value | Language |
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dc.contributor.author | Kyung Sun Hwang | - |
dc.contributor.author | Won-Kyung Cho | - |
dc.contributor.author | Jin Sang Yoo | - |
dc.contributor.author | Y R Seong | - |
dc.contributor.author | B K Kim | - |
dc.contributor.author | S Y Kim | - |
dc.contributor.author | Dong Soo Im | - |
dc.date.accessioned | 2017-04-19T09:01:25Z | - |
dc.date.available | 2017-04-19T09:01:25Z | - |
dc.date.issued | 2004 | - |
dc.identifier.issn | 0929-1903 | - |
dc.identifier.uri | 10.1038/sj.cgt.7700711 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/6614 | - |
dc.description.abstract | We 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.publisher | Springer-Nature Pub Group | - |
dc.title | 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 | - |
dc.title.alternative | 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 | - |
dc.type | Article | - |
dc.citation.title | Cancer Gene Therapy | - |
dc.citation.number | 6 | - |
dc.citation.endPage | 407 | - |
dc.citation.startPage | 397 | - |
dc.citation.volume | 11 | - |
dc.contributor.affiliatedAuthor | Kyung Sun Hwang | - |
dc.contributor.affiliatedAuthor | Won-Kyung Cho | - |
dc.contributor.affiliatedAuthor | Jin Sang Yoo | - |
dc.contributor.affiliatedAuthor | Dong Soo Im | - |
dc.contributor.alternativeName | 황경선 | - |
dc.contributor.alternativeName | 조원경 | - |
dc.contributor.alternativeName | 유진상 | - |
dc.contributor.alternativeName | 성영림 | - |
dc.contributor.alternativeName | 김범경 | - |
dc.contributor.alternativeName | 김삼용 | - |
dc.contributor.alternativeName | 임동수 | - |
dc.identifier.bibliographicCitation | Cancer Gene Therapy, vol. 11, no. 6, pp. 397-407 | - |
dc.identifier.doi | 10.1038/sj.cgt.7700711 | - |
dc.subject.keyword | Adenovirus vector | - |
dc.subject.keyword | IL-18 mutant | - |
dc.subject.keyword | Liver cancer | - |
dc.subject.keyword | Renal cancer | - |
dc.subject.local | adenovirus vector | - |
dc.subject.local | Adenovirus vector | - |
dc.subject.local | IL-18 mutant | - |
dc.subject.local | Liver cancer | - |
dc.subject.local | liver cancer | - |
dc.subject.local | Liver Cancer | - |
dc.subject.local | Renal cancer | - |
dc.description.journalClass | Y | - |
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