Diagnostic and therapeutic application of telomerase-specific oncolytic adenoviral agents

Toshiyoshi Fujiwara, Yasuo Urata, Noriaki Tanaka

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site (IRES). Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. We further modified the E3 region of OBP-301 to contain green fluorescent protein (GFP) gene for monitoring viral replication (TelomeScan, OBP-401). When TelomeScan was intratumorally injected into human tumors orthotopically implanted into the rectum in mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. Our results indicate that TelomeScan causes viral spread into the regional lymphatic area and selectively replicates in neoplastic lesions, resulting in GFP expression in metastatic lymph nodes. This article reviews recent highlights in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the telomerase-specific oncolytic adenoviruses.

Original languageEnglish
Pages (from-to)1881-1886
Number of pages6
JournalFrontiers in Bioscience
Volume13
Issue number5
DOIs
Publication statusPublished - 2008

Fingerprint

Telomerase
Tumors
Cells
Neoplasms
Genes
Green Fluorescent Proteins
Viruses
Viral Genes
Therapeutics
Adenoviridae
Lymph Nodes
Cytotoxicity
Oncogenic Viruses
Chemical activation
Cameras
Rectum
Laparotomy
Color
Carcinogenesis
Monitoring

Keywords

  • Adenovirus
  • GFP; imaging
  • hTERT
  • Review
  • Telomerase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Medicine(all)

Cite this

Diagnostic and therapeutic application of telomerase-specific oncolytic adenoviral agents. / Fujiwara, Toshiyoshi; Urata, Yasuo; Tanaka, Noriaki.

In: Frontiers in Bioscience, Vol. 13, No. 5, 2008, p. 1881-1886.

Research output: Contribution to journalArticle

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