Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12

Hepatology. 2001 Jan;33(1):52-61. doi: 10.1053/jhep.2001.20796.


The use of gene therapy to enhance antitumor immunity has emerged as a promising procedure to fight cancer. In this study we have tested the ability of an adenovirus carrying interleukin 12 (IL-12) gene (AdCMVIL-12) to eliminate tumoral lesions in 3 animal models of orthotopic hepatocellular carcinoma (HCC). Intratumoral injection of AdCMVIL-12 in animals with a single big tumor nodule implanted in the liver resulted in significant inhibition of tumor growth in a dose-dependent manner. Fifty percent of animals that received a dose of 5 x 10(9) plaque-forming units, showed complete regression of the tumor 2 weeks after treatment. In animals with 2 independent tumor nodules in the left liver lobe, injection in only one of them of 5 x 10(9) pfu AdCMVIL-12 induced, 15 days after therapy, complete regression of 50% of treated tumors and also of 50% of untreated lesions, with 60% long-term survival. Rats that were tumor free after therapy with AdCMVIL-12 showed protection against tumor rechallenge. A group of rats received the carcinogen diethylnitrosamine and developed multiple hepatic dysplasic nodules of 1 to 5 mm in diameter. These animals were treated by intrahepatic artery injection of either AdCMVIL-12 (5 x 10(9) pfu) or control vector. In this model AdCMVIL-12 induced complete tumor regression in 20% of treated rats and inhibited tumor growth in 60% of cases with an increase in rat survival. Activation of natural killer (NK) cells and inhibition of angiogenesis were found to be antitumor mechanisms set in motion by AdCMVIL-12. Our data indicate that experimental HCC can be efficiently treated by intratumoral or intravascular injection of adenovirus expressing IL-12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Carcinogens
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line
  • Diethylnitrosamine
  • Genetic Therapy*
  • Injections, Intralesional
  • Interleukin-12 / genetics*
  • Killer Cells, Natural / physiology
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / therapy*
  • Male
  • Neoplasms, Multiple Primary / therapy
  • Neovascularization, Pathologic / prevention & control
  • Rats
  • Rats, Inbred BUF
  • Rats, Wistar


  • Carcinogens
  • Interleukin-12
  • Diethylnitrosamine