Adenovirus-mediated gene transfer of pathogen-associated molecular patterns for cancer immunotherapy.

Tosch, C; Geist, M; Ledoux, C; Ziller-Remi, C; Paul, S; Erbs, P; Corvaia, N; Von Hoegen, P; Balloul, J-M; Haegel, H

Tosch, C; Geist, M; Ledoux, C; Ziller-Remi, C; Paul, S; Erbs, P; Corvaia, N; Von Hoegen, P; Balloul, J-M; Haegel, H.

Afiliación

Tosch C; Molecular Immunology Department, Transgene, Strasbourg, France.

Cancer Gene Ther ; 16(4): 310-9, 2009 Apr.

Article en En | MEDLINE | ID: mdl-18949016

RESUMEN

The delivery of stimulatory signals to dendritic cells (DCs) in the tumor microenvironment could be an effective means to break tumor-induced tolerance. The work presented here evaluates the immunostimulatory properties of pathogen-associated molecular patterns (PAMPs), microbial molecules which bind Toll-like receptors and deliver activating signals to immune cells, when expressed in tumor cells using adenoviral (Ad) vectors. In vitro, transduction of A549 tumor cells with Ad vectors expressing either flagellin from Listeria monocytogenes or P40 protein from Klebsiella pneumoniae induced the maturation of human monocyte-derived DCs in co-cultures. In mixed lymphocyte reactions (MLRs), Ad-flagellin and Ad-P40 transduction of tumor cells stimulated lymphocyte proliferation and the secretion of IFN-gamma. In vivo, these vectors were used either as stand-alone immunoadjuvants injected intratumorally or as vaccine adjuvants combined with a tumor antigen-expressing vector. When Ad-PAMPs were administered intratumorally to mice bearing subcutaneous syngeneic B16F0-CAR (cocksackie-adenovirus receptor) melanomas, tumor progression was transiently inhibited by Ad-P40. In a therapeutic vaccine setting, the combination of Ad-MUC1 and Ad-PAMP vectors injected subcutaneously delayed the growth of implanted RenCa-MUC1 tumors and improved tumor rejection when compared with vaccination with Ad-MUC1 alone. These results suggest that Ad-PAMPs could be effective immunoadjuvants for cancer immunotherapy.

Asunto(s)

Adenoviridae/genética; Proteínas de la Membrana Bacteriana Externa/inmunología; Terapia Genética; Proteína HN/inmunología; Inmunoterapia; Neoplasias/terapia; Animales; Proteínas de la Membrana Bacteriana Externa/biosíntesis; Proteínas de la Membrana Bacteriana Externa/genética; Línea Celular Tumoral; Técnicas de Cocultivo; Citocinas/biosíntesis; Células Dendríticas/patología; Células Dendríticas/fisiología; Femenino; Técnicas de Transferencia de Gen; Vectores Genéticos; Proteína HN/biosíntesis; Proteína HN/genética; Humanos; Activación de Linfocitos; Ratones; Neoplasias/genética; Neoplasias/inmunología; Virus de la Enfermedad de Newcastle/genética

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de la Membrana Bacteriana Externa / Terapia Genética / Proteína HN / Adenoviridae / Inmunoterapia / Neoplasias Tipo de estudio: Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Gene Ther Asunto de la revista: GENETICA MEDICA / NEOPLASIAS / TERAPEUTICA Año: 2009 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

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