Gene therapy for hepatocellular carcinoma: Long-term remission of primary and metastatic tumors in mice by interleukin-2 gene therapy in vivo

H. Huang, S. H. Chen, K. Kosai, M. J. Finegold, S. L C Woo

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

To explore gene therapy as a new treatment modality for hepatocellular carcinoma, a pre-clinical animal model was established by intrahepatic implantation of a mouse hepatocellular carcinoma cell lime (MH134) in syngeneic recipients. The resulting hepatic tumors were treated with a recombinant adenoviral vector expressing the murine interleukin-2 (IL-2) gene, and long-term remission was achieved in 50% of the animals. The remaining animals died of malignant ascites, which also occurs in some human patients. Those animals were treated with a second dose of the recombinant adenoviral vector by direct inoculation into the peritoneal cavity, and long-term remission of the disseminated disease was achieved in 55% of the animals. Thus, a combined cure rate of greater than 75% for primary and disseminated hepatocellular carcinoma was achieved by successive adenovirus-mediated IL-2 gene treatments. Histopathological and immunocytochemical analyses showed massive infiltration of the tumor by macrophages and T lymphocytes in IL-2 vector treated animals. The surviving animals developed systemic antitumoral cellular immunity that protected them against challenges of parental hepatoma cells implanted at distant sites. The results suggest that IL-2 gene therapy may be a strategy applicable for the treatment of both primary and metastatic hepatocellular carcinomas in man.

Original languageEnglish (US)
Pages (from-to)980-987
Number of pages8
JournalGene Therapy
Volume3
Issue number11
StatePublished - Dec 9 1996

Keywords

  • Adenovirus vector
  • Gene therapy
  • Hepatocellular carcinoma
  • Interleukin 2
  • Systemic antitumoral immunity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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