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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología terapia génica > DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista >

Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12
Autor(es) : Barajas, M. (Miguel)
Mazzolini, G. (Guillermo)
Genove, G. (Guillem)
Bilbao, R. (Roberto)
Narvaiza, I. (Íñigo)
Schmitz, V. (Volker)
Sangro, B. (Bruno)
Melero, I. (Ignacio)
Qian, C. (Cheng)
Prieto, J. (Jesús)
Palabras clave : Adenoviridae/genetics
Carcinoma, Hepatocellular/therapy
Gene Therapy
Interleukin-12/genetics
Liver Neoplasms/therapy
Fecha incorporación: 2001
Editorial : Wiley Blackwell
Versión del editor: http://bit.ly/rRDfFv
ISSN: 1527-3350
Cita: Barajas M, Mazzolini G, Genove G, Bilbao R, Narvaiza I, Schmitz V, et al. Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12. Hepatology 2001 Jan;33(1):52-61.
Resumen
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.
Enlace permanente: http://hdl.handle.net/10171/20410
Aparece en las colecciones: DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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