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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 >

Adenoviral gene transfer of interleukin 12 into tumors synergizes with adoptive T cell therapy both at the induction and effector level
Authors: Mazzolini, G. (Guillermo)
Qian, C. (Cheng)
Narvaiza, I. (Íñigo)
Barajas, M. (Miguel)
Borras-Cuesta, F. (Francisco)
Xie, X. (Xiaoming)
Duarte, M. (Marina)
Melero, I. (Ignacio)
Prieto, J. (Jesús)
Keywords: Adenoviridae/genetics
Gene Transfer Techniques
Immunotherapy, Adoptive
Interleukin-12/genetics
T-Lymphocytes, Cytotoxic/immunology
Issue Date: 2000
Publisher: Mary Ann Liebert
Publisher version: http://online.liebertpub.com/doi/abs/10.1089/10430340050016201
ISSN: 1557-7422
Citation: Mazzolini G, Qian C, Narvaiza I, Barajas M, Borras-Cuesta F, Xie X, et al. Adenoviral gene transfer of interleukin 12 into tumors synergizes with adoptive T cell therapy both at the induction and effector level. Hum Gene Ther 2000 Jan 1;11(1):113-125.
Abstract
Tumors infected with a recombinant defective adenovirus expressing interleukin 12 (IL-12) undergo regression, associated with a cytotoxic T lymphocyte (CTL)-mediated antitumor immune response. In the present study we generated anti-CT26 CTLs by short-term coculture of CT26 cells and lymph node cells obtained from mice harboring subcutaneous CT26 tumors injected with an adenoviral vector expressing IL-12 (AdCMVIL-12), control adenovirus (AdCMVlacZ), or saline. Regression of small intrahepatic CT26 tumors in unrelated syngeneic animals was achieved with CTLs derived from mice whose subcutaneous tumors had been injected with AdCMVIL-12 but not with CTLs from the other two control groups. The necessary and sufficient effector cell population for adoptive transfer consisted of CD8+ T cells that showed anti-CT26 specificity partly directed against the AH1 epitope presented by H-2Ld. Interestingly, treatment of a subcutaneous tumor nodule with AdCMVIL-12, combined with intravenous adoptive T cell therapy with short-term CTL cultures, had a marked synergistic effect against large, concomitant live tumors. Expression of IL-12 in the liver in the vicinity of the hepatic tumor nodules, owing to spillover of the vector into the systemic circulation, appeared to be involved in the increased in vivo antitumor activity of injected CTLs. In addition, adoptive T cell therapy improved the outcome of tumor nodules transduced with suboptimal doses of AdCMVIL-12. Our data provide evidence of a strong synergy between gene transfer of IL-12 and adoptive T cell therapy. This synergy operates both at the induction and effector phases of the CTL response, thus providing a rationale for combined therapeutic strategies for human malignancies.
Permanent link: http://hdl.handle.net/10171/21736
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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