title: In vivo electroporation restores the low effectiveness of DNA vaccination against HER-2/neu in aging.
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.
authors.affiliation: Advanced Technology Center for Aging Research, Scientific Technological Area, INRCA-IRCCS, Via Birarelli 8, 60121, Ancona, Italy. m.provinciali@inrca.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
authors.forename: Alessandra
authors.initials: A
authors.lastname: Barucca
authors.forename: Elisa
authors.initials: E
authors.lastname: Pierpaoli
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Sara
authors.initials: S
authors.lastname: Pierpaoli
authors.forename: Arianna
authors.initials: A
authors.lastname: Smorlesi
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D018274:Electroporation / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology; D007273:Injections, Intramuscular; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA