(1) Advanced Technology Center for Aging Research, Scientific Technological Area, INRCA-IRCCS, Via Birarelli 8, 60121 Ancona, Italy
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.