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Artículo

A Novel Synergistic Combination of Cyclophosphamide and Gene Transfer of Interleukin-12 Eradicates Colorectal Carcinoma in Mice

Malvicini, MarianaIcon ; Rizzo, Manglio MiguelIcon ; Alaniz, Laura; Piñero, Federico; García, Mariana GabrielaIcon ; Atorrasagasti, María CatalinaIcon ; Aquino, Jorge BenjaminIcon ; Rozados, Viviana RosaIcon ; Scharovsky, Olga GracielaIcon ; Matar, PabloIcon ; Mazzolini Rizzo, Guillermo DanielIcon
Fecha de publicación: 12/2009
Editorial: American Association for Cancer Research
Revista: Clinical Cancer Research
ISSN: 1078-0432
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Oncología

Resumen

Purpose: Interleukin-12 (IL-12) is an immunostimulatory cytokine with potent antitumor effects in several animal models. However, serious toxicity has been associated with its systemic application in humans. Gene transfer has emerged as a tool to specifically express therapeutic genes into the tumor/peritumoral milieu, thus avoiding systemic toxicity. The aim of this study was to analyze whether subtherapeutic doses of an adenovirus encoding IL-12 (AdIL-12) might synergize with low immunopotentiating doses of cyclophosphamide in the treatment of colorectal carcinoma. Experimental Design: The antitumor effect of combining a single low dose of cyclophosphamide with an intratumoral injection of AdIL-12 was evaluated in an in vivo murine colorectal carcinoma model. The immune responses achieved with different treatments were monitored, comparing the effect of combining both therapies with individual treatments. Results: The combined therapy induced a complete tumor regression in >50% of mice in a synergistic fashion, and it significantly prolonged their survival. This strategy was superior to each single treatment in reducing both peripheral and splenic CD4+CD25+Foxp3+ regulatory T cells, increasing the number of activated dendritic cells, and inducing IFNγ-secreting CD4-positive T lymphocytes. Importantly, the combined treatment generated a powerful tumor-specific CTL response. Consistently, a significant reduction in IL-10 levels was found. Our data suggest that the combination of nontoxic doses of cyclophosphamide with AdIL-12 allows the generation of good antitumoral responses, thus avoiding undesired side effects of both agents. Conclusions: Our data strongly support the use of a combination of cyclophosphamide and AdIL-12 as a novel therapeutic strategy against colorectal carcinoma. (Clin Cancer Res 2009;15(23):7256–65)
Palabras clave: Cyclophosphamide , IL12 , Colorectal Carcinoma
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/254941
URL: https://aacrjournals.org/clincancerres/article/15/23/7256/74478/A-Novel-Synergis
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-09-1861
Colecciones
Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Citación
Malvicini, Mariana; Rizzo, Manglio Miguel; Alaniz, Laura; Piñero, Federico; García, Mariana Gabriela; et al.; A Novel Synergistic Combination of Cyclophosphamide and Gene Transfer of Interleukin-12 Eradicates Colorectal Carcinoma in Mice; American Association for Cancer Research; Clinical Cancer Research; 15; 23; 12-2009; 7256-7265
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