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

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

Research output: Contribution to journalArticle

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-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.

Original languageEnglish
Pages (from-to)462-472
Number of pages11
JournalCancer Gene Therapy
Volume16
Issue number5
DOIs
Publication statusPublished - May 2009

Keywords

  • Adjuvant
  • BALB-neuT
  • Cancer vaccine
  • CEA
  • TLR7

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models'. Together they form a unique fingerprint.

Cite this