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E1A/E1B 이중변이형 종양 선택적 살상 아데노바이러스의 개선된 암세포 살상 효과 및 항종양 효과

Other Titles
 Enhanced Oncolytic Effect and Anti-Tumor Effect of Replication Competent Adenovirus with Double Mutation in E1A & E1B Regions 
Authors
 김재성  ;  최경주  ;  김평환  ;  김주항  ;  손주혁  ;  윤채옥 
Citation
 Journal of Bacteriology and Virology, Vol.35(2) : 113-124, 2005 
Journal Title
 Journal of Bacteriology and Virology 
ISSN
 1598-2467 
Issue Date
2005
Abstract
Gene-modified replication-competent adenoviruses (Ads) are emerging as a promising new modality for the treatment of cancer. We have previously shown that E1B 19kDa and E1B 55kDa gene deleted Ad (Ad-△E1B19/55) exhibits improved tumor-specific replication and cell lysis, leading to potent anti-tumor effect. As an additional effort to increase cancer cell-selectivity of replicating adenovirus, we have first generated eleven E1A-mutant Ads (Ad-mt#1~#11) with deletion or substitution in retinoblastoma (Rb) binding sites of E1A. Of these viruses, Ad-mt#7, demonstrated Significantly improved cytopathic effect (CPE) and viral replication in a cancer cell-specific manner. To further increase the cancer cell-specific killing effect of Ad-mt#7, both E1B 19kDa and E1B 55kDa genes were deleted, resulting in an Ad-△E1Bmt7. As assessed using CPE assay, MTT assay, and immunoblot analysis for Ad fiber expression, Ad-△E1Bmt7 exerted markeldly enhanced cancer cell-specific killing effect as well as viral replication in comparison to either Ad-mt#7 or Ad-△E1B19/55. Furthermore, the growth of established human cervical carcinoma in nude mice was significantly suppressed by intratumoral injection of Ad-△E1Bmt7. In summary, we have developed an oncolytic adenovirus with significantly improved therapeutic profiles for cancer treatment.
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Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
김재성(Kim, Jaesung)
김주항(Kim, Joo Hang)
김평환(Kim, Pyung Hwan)
손주혁(Sohn, Joo Hyuk) ORCID logo https://orcid.org/0000-0002-2303-2764
윤채옥(Yun, Chae Ok)
최경주(Choi, Kyung Ju)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147319
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