Gene Therapy for Hepatocellular Carcinoma: Long-Term Remission of Primary and Metastatic Tumors in Mice by interleukin-2 Gene Therapy in Vivo

Gene Ther. 1996 Nov;3(11):980-7.

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 line (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Carcinoma, Hepatocellular / therapy*
  • Gene Expression
  • Genetic Therapy*
  • Genetic Vectors*
  • Humans
  • Injections, Intraperitoneal
  • Interleukin-2 / genetics*
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Metastasis
  • Neoplasms, Experimental / therapy*
  • Tumor Cells, Cultured

Substances

  • Interleukin-2