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An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models

Cancer Gene Therapy volume 16, pages 462–472 (2009)Cite this article

Abstract

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 α (IFNα) 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-p185neu 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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Acknowledgements

This study was funded by Ministero dell’Istruzione, dell’Università e della Ricerca; Grant number FIRB RBME017BC4. We acknowledge Dr Guido Forni for BALB-neuT mice, Drs C Bentsen, I Pak, A Fridman and A Bagchi for statistical analysis, M Emili for graphics and J Clench for editorial assistance.

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Authors and Affiliations

  1. Department of Oncology and Pharmacology, IRBM P Angeletti, Pomezia, Italy

    S Dharmapuri, L Aurisicchio, P Neuner, M Verdirame, G Ciliberto & N La Monica

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  1. S Dharmapuri
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Correspondence to N La Monica.

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Dharmapuri, S., Aurisicchio, L., Neuner, P. et al. An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models. Cancer Gene Ther 16, 462–472 (2009). https://doi.org/10.1038/cgt.2008.91

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