PMID: 8940638Nov 1, 1996Paper

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

Gene Therapy
H HuangS L Woo

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 t...Continue Reading

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