In vivo electroporation restores the low effectiveness of DNA vaccination against HER-2/neu in aging

Mauro Provinciali, Alessandra Barucca, Elisa Pierpaoli, Fiorenza Orlando, Sara Pierpaoli, Arianna Smorlesi

Research output: Contribution to journalArticle

Abstract

Experimental evidence has been provided that cancer vaccines are less effective at older age than in young adults. In this study, we evaluated the possibility to recover the low effectiveness of DNA immunization against HER-2/neu increasing plasmid uptake by cells from old mice through electroporation with the aim to enhance the activation of specific immune responses. Young and old Balb/c mice received two immunizations with a pCMV-ECDTM DNA plasmid using plasmid intramuscular injection followed by electroporation (IM + E) or plasmid intramuscular injection alone (IM), and successively, they were challenged with syngeneic HER-2/neu overexpressing TUBO cells. Young mice were completely protected whereas less than 60% protection was observed in old mice after IM immunization. IM + E immunization completely protected old mice against a TUBO cell challenge. The protection was associated with increased transgene expression in the site of immunization and with the induction of both humoral and cell-mediated immunity in old mice. We conclude that the effectiveness of anticancer DNA vaccination in old ages may be improved increasing plasmid uptake and transgene expression through electroporation, suggesting the relevant role of the first steps of the immunization process in the success of cancer vaccines at older age.

Original languageEnglish
Pages (from-to)363-371
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • Aging
  • DNA vaccination
  • Electroporation
  • HER-2/neu

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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