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

16 Citations (Scopus)

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

Fingerprint

Transgenic Mice
Vaccination
DNA
Neoplasms
Vaccines
Plasmids
Immunologic Adjuvants
DNA Vaccines
Electroporation
Tumor Cell Line
Colonic Neoplasms
Interferons
SM360320
Immunoglobulin G
Breast Neoplasms
Antigens
Antibodies
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models. / Dharmapuri, S.; Aurisicchio, L.; Neuner, P.; Verdirame, M.; Ciliberto, G.; La Monica, N.

In: Cancer Gene Therapy, Vol. 16, No. 5, 05.2009, p. 462-472.

Research output: Contribution to journalArticle

Dharmapuri, S, Aurisicchio, L, Neuner, P, Verdirame, M, Ciliberto, G & La Monica, N 2009, 'An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models', Cancer Gene Therapy, vol. 16, no. 5, pp. 462-472. https://doi.org/10.1038/cgt.2008.91
Dharmapuri, S. ; Aurisicchio, L. ; Neuner, P. ; Verdirame, M. ; Ciliberto, G. ; La Monica, N. / An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models. In: Cancer Gene Therapy. 2009 ; Vol. 16, No. 5. pp. 462-472.
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