期刊
CANCER GENE THERAPY
卷 16, 期 5, 页码 462-472出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2008.91
关键词
cancer vaccine; TLR7; adjuvant; CEA; BALB-neuT
类别
资金
- Ministero dell'Istruzione
- dell'Universita e della Ricerca [FIRB RBME017BC4]
In vivo electroporation of plasmid DNA (DNA-EP) is an efficient and safe method for vaccines resulting in increased DNA uptake, enhanced protein expression and increased immune responses to the target antigen in a variety of species. To further enhance the efficacy of DNA-EP, we have evaluated the toll-like receptor7 (TLR7) agonist-2, 9, substituted 8-hydroxyadenosine derivative or SM360320-as an adjuvant to vaccines against HER2/neu and CEA in BALB-neuT and CEA transgenic mice (CEA. Tg), respectively. SM360320 induced in vivo secretion of interferon alpha (IFN alpha) and exerted a significant antitumor effect in CEA. Tg mice challenged with a syngenic tumor cell line expressing CEA and an additive effect with a CEA vaccine. Additionally, combination of SM360320 with plasmid encoding the extracellular and transmembrane domain of ratHER2/neu affected the spontaneous tumor progression in BALB-neuT mice treated in an advanced disease setting. The antitumor effect in mice treated with DNA-EP and SM360320 was associated with an anti-CEA and anti- p185(neu) antibody isotype switch from IgG1 to IgG2a. These data demonstrate that SM360320 exerts significant antitumor effects and can act in association with DNA-EP for CEA-positive colon cancer and HER2-positive mammary carcinoma. These observations therefore emphasize the potential of SM360320 as immunological adjuvant for therapeutic DNA vaccines.
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