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

Ho Yeong Lim, Miwon Ahn, Hyun Cheol Chung, Thomas Gardner, Chinghai Kao, Sang Jin Lee, Se Joong Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)532-538
Number of pages7
JournalCancer Gene Therapy
Volume11
Issue number8
DOIs
StatePublished - Aug 2004

Fingerprint

Adenoviridae
Uterine Cervical Neoplasms
Genetic Therapy
Neoplasms
Growth
HeLa Cells
Nude Mice
Cervix Uteri
Glycoproteins
Proteins
Carcinoma
Cell Line
Injections
Infection
Therapeutics

Keywords

  • Adenovirus
  • Cervix neoplasms
  • MN/CA9
  • Virus replication

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus. / Lim, Ho Yeong; Ahn, Miwon; Chung, Hyun Cheol; Gardner, Thomas; Kao, Chinghai; Lee, Sang Jin; Kim, Se Joong.

In: Cancer Gene Therapy, Vol. 11, No. 8, 08.2004, p. 532-538.

Research output: Contribution to journalArticle

Lim, Ho Yeong ; Ahn, Miwon ; Chung, Hyun Cheol ; Gardner, Thomas ; Kao, Chinghai ; Lee, Sang Jin ; Kim, Se Joong. / Tumor-specific gene therapy for uterine cervical cancer using MN/CA9-directed replication-competent adenovirus. In: Cancer Gene Therapy. 2004 ; Vol. 11, No. 8. pp. 532-538.
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