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Increased Cytopathic Effect of Replicating Adenovirus Expressing Adenovirus Death Protein

Authors
 Eunhee Kim  ;  Joo Hang Kim  ;  Chae Ok Yun  ;  Joo Hyuk Sohn  ;  Taeyoung Koo 
Citation
 Cancer Research and Treatment, Vol.35(5) : 425-432, 2003 
Journal Title
 Cancer Research and Treatment 
ISSN
 1598-2998 
Issue Date
2003
Abstract
PURPOSE: Replication-competent adenoviruses (Ads) are promising new modalities for the treatment of cancer. Selective replication of a viral agent in tumor may lead to improved efficacy over non-replicating Ads due to viral multiplication, lysis of the infected cancer cell and spread to surrounding cells. In our previous studies it was shown that the E1B 55 kD-deleted Ad (YKL-1) exhibits tumor specific replication and cell lysis, but with reduced cytolytic effects compared to the wild type adenovirus (Int J Cancer 2000;88: 454-463). Thus, improving the potency of oncolytic Ads remains an important goal for cancer gene therapy. To increase the oncolytic ability of YKL-1, an adenovirus death protein (ADP) gene was reintroduced under the control of a CMV or MLP promoter at the E3 region of the YKL-1, generating an YKL-cADP and YKL-mADP, respectively. MATERIALS AND METHODS: The in vitro cytolytic effect of ADP expressing Ads was evaluated by MTT assay, and the induction of apoptosis by ADP expressing Ads was examined by TUNEL analysis. Finally, the antitumor effect of ADP expressing Ads was demonstrated in C33A xenograft tumor model. RESULTS: The YKL-cADP exerted a markedly enhanced cytolytic effect against H460 and SK-Hep1 cancer cell lines. The TUNEL assay indicated that the ADP-mediated cytotoxicity was largely driven by apoptosis. Finally, the YKL-cADP showed a superior antitumor effect than the YKL-1 or YKL-mADP in C33A xenografts. CONCLUSION: These lines of evidence demonstrate that the YKL-cADP induces efficient cell lysis, which is critical for the addition of therapeutic value to replicating Ads in cancer gene therapy.
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Appears in Collections:
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
김주항(Kim, Joo Hang)
손주혁(Sohn, Joo Hyuk) ORCID logo https://orcid.org/0000-0002-2303-2764
윤채옥(Yun, Chae Ok)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114128
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