Regression of colon cancer and induction of antitumor immunity by intratumoral injection of adenovirus expressing interleukin-12

Interleukin-12 (IL-12) has been shown to possess potent immunoregulatory and antitumoral effects. We have evaluated the anti-oncogenic potential and the mechanisms of the antitumoral effect of in vivo adenovirus-mediated transfer of IL-12 gene in a murine model of colon cancer. AdCMVIL-12 was constr...

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Detalles Bibliográficos
Autores: Mazzolini, G. (Guillermo)|||/items/73a250e4-d50b-45d7-bf6b-f222192f702e, Qian, C. (Cheng)|||/items/49f586b0-dcc7-4e30-82f4-91f3c38ecc37, Xie, X. (Xiaoming)|||/items/827cb7cc-fd00-4608-a7ad-99768c3c215f, Sun, Y. (Yonglian)|||/items/0b092e80-f3f5-4924-a056-26006aab1615, Lasarte-Sagastibelza, J.J. (Juan José)|||/items/e366ad83-3db4-41ec-a9da-ed9159ba5c0c, Drozdzik, M. (Marek)|||/items/f94b6eeb-69fa-4e8b-99d1-a67fed00a236, Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71
Tipo de recurso: artículo
Fecha de publicación:1999
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/21724
Acceso en línea:https://hdl.handle.net/10171/21724
Access Level:acceso abierto
Palabra clave:Gene therapy
Adenovirus
Interleukin-12
Colon cancer
Animal mode
Cytotoxicity
Descripción
Sumario:Interleukin-12 (IL-12) has been shown to possess potent immunoregulatory and antitumoral effects. We have evaluated the anti-oncogenic potential and the mechanisms of the antitumoral effect of in vivo adenovirus-mediated transfer of IL-12 gene in a murine model of colon cancer. AdCMVIL-12 was constructed to permit coordinated production of p40 and p35 subunits of IL-12 gene to obtain the maximum IL-12 bioactivity. Infection of murine colon cancer CT-26 cells in vitro with AdCMVIL-12 resulted in the production of high levels of IL-12. In vivo gene therapy of colon cancer nodules by intratumoral injection of AdCMVIL-12 induced a local increase in IL-12 and interferon-gamma levels and a complete regression of the tumor in 26 of 34 (76%) mice. Tumor disappeared between days 7 and 10 after vector administration. The antitumoral effect was mediated by CD8+ T cells and was associated with the generation of cytotoxic T lymphocytes against colon cancer cells. Animals that eliminated the tumor were protected against a second administration of neoplastic cells. Treatment with AdCMVIL-12 of one tumor nodule also caused regression of established tumors at distant sites. These data demonstrate that AdCMVIL-12 is a useful therapeutic tool for established colon cancer in mice and should be considered for application in humans.

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