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Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus

 Ho Yeong Lim  ;  Miwon Ahn  ;  Hyun Cheol Chung  ;  Thomas A Gardner  ;  Chinghai Kao  ;  Sang-Jin Lee  ;  Se Joong Kim 
 CANCER GENE THERAPY, Vol.11(8) : 532-538, 2004-08 
Journal Title
Issue Date
Adenoviridae / genetics* ; Adenovirus E1A Proteins / biosynthesis ; Adenovirus E1A Proteins / genetics ; Animals ; Antigens, Neoplasm / genetics* ; Antigens, Neoplasm / metabolism ; Carbonic Anhydrase IX ; Carbonic Anhydrases / genetics* ; Carbonic Anhydrases / metabolism ; Female ; Gene Expression ; Genetic Therapy / methods* ; Genetic Vectors / genetics ; HeLa Cells ; Humans ; Mice ; Promoter Regions, Genetic / genetics ; RNA, Messenger / analysis ; RNA, Messenger / metabolism ; Uterine Cervical Neoplasms / genetics ; Uterine Cervical Neoplasms / metabolism ; Uterine Cervical Neoplasms / therapy* ; Virus Replication / genetics ; Xenograft Model Antitumor Assays
Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 protein is highly expressed in uterine cervical cancer tissues, but not in normal cervix, we constructed a tumor-specific replication-competent adenoviral vector utilizing MN/CA9 promoter (Ad-MN/CA9-E1a), which can replicate only in MN/CA9-expressing cells. Infection of Ad-MN/CA9-E1a to MN/CA9-positive uterine cervical cancer cells (HeLa, C-33 A and SiHa) resulted in much stronger Ad5 E1a protein expressions compared with MN/CA9-negative cells (SK-RC-29), suggesting a tissue-specific replication of this recombinant adenovirus. In vitro cytotoxicity assay revealed that the growth of MN/CA9-positive cells was significantly inhibited with 0.01-1 MOI of Ad-MN/CA9-E1a, but the growth of MN/CA9-negative cells (SK-RC-29) could only be inhibited by as many as 100 MOI. Intratumoral injection of Ad-MN/CA9-E1a effectively induced growth delay of HeLa tumors in nude mice. These results suggest that a novel replication-competent adenoviral vector mediated by MN/CA9 promoter, Ad-MN/CA9-E1a, can selectively replicate in MN/CA9-expressing tumors with cytotoxic effects and may be utilized for the treatment of uterine cervical cancer.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
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