Gene therapy for hepatocellular carcinoma: long-term remission of primary and metastatic tumors in mice by interleukin-2 gene therapy in vivo.
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.
Huang
H
H
Department of Cell Biology, Baylor College of Medicine, Houston, TX, USA.
Chen
S H
SH
Kosai
K
K
Finegold
M J
MJ
Woo
S L
SL
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000628:therapy*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2