Target gene therapy for α-fetoprotein-producing hepatocellular carcinoma by E1B55k-attenuated adenovirus

Makoto Ohashi, Fumihiko Kanai, Keisuke Tateishi, Hiroyoshi Taniguchi, Paola A. Marignani, Yoko Yoshida, Yasushi Shiratori, Hirofumi Hamada, Masao Omata

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Gene therapy using replication-competent adenovirus that selectively propagates in tumor cells may be an effective treatment for cancer. We developed an adenovirus that would be replication specific for hepatocellular carcinoma (HCC). Based on our finding that the E1B55k-deficient adenovirus was able to replicate in human primary hepatocytes, we therefore designed an adenovirus carrying E1A and attenuated E1B gene driven by the α-fetoprotein promoter (Adv-AFP-E1AdB), thus restricting the replication specificity in AFP-producing HCC. Replication of Adv-AFP-E1AdB in primary hepatocytes was practically negligible 4 days after infection. Although Adv-AFP-E1AdB replicated slowly in AFP-producing HCC, it efficiently destroyed HCC cells independent of their p53 status. Experiments were conducted in vivo using systemic administration of Adv-AFP-E1AdB and we observed tumor size reduction in nude mice having liver cancer. The use of replication-competent adenovirus deficient of the E1B gene coupled to an AFP-targeting strategy may be a safe and efficacious treatment for HCC.

Original languageEnglish
Pages (from-to)529-535
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume282
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. S. Fukuda for technical assistance with the electron microscopic study, S. Satoh for technical assistance with the animal study, and R. Sato for technical assistance with the cell culture. This work was supported in part by grants from the Ministry of Health and Welfare and the Ministry of Education, Culture and Science, Japan.

ASJC Scopus Subject Areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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