A multi-DNA preventive vaccine for p53/neu-driven cancer syndrome

C. De Giovanni, G. Nicoletti, A. Palladini, S. Croci, L. Landuzzi, A. Antognoli, A. Murgo, A. Astolfi, S. Ferrini, M. Fabbi, A. M. Orengo, A. Amici, M. L. Penichet, L. Aurisicchio, M. Iezzi, P. Musiani, P. Nanni, P. L. Lollini

Research output: Contribution to journalArticlepeer-review

Abstract

The highly aggressive cancer syndrome of female mice carrying a p53 knockout allele and a rat HER-2/neu (Neu) transgene (BALB-p53Neu) can be prevented by a cell vaccine presenting three components: Neu, interleukin (IL)-12 production, and allogeneic major histocompatibility complex (MHC) alleles (Triplex cell vaccine). Here we tested a second-generation Triplex DNA-based vaccine (Tri-DNA), consisting of the combination of three gene components (a transmembrane-extracellular domain fragment of the Neu gene, IL-12 genes, and the H-2Dq allogeneic MHC gene), carried by separate plasmids. The Tri-DNA vaccine was at least as effective as the Triplex cell vaccine for cancer immunoprevention, giving a similar delay in the onset of mammary cancer and complete protection from salivary cancer. Both vaccines induced anti-Neu antibodies of the murine IgG2a isotype at similar levels. The Tri-DNA vaccine gave more restricted immunostimulation, consisting of a fully helper T cell type 1 (Th1)-polarized response, with effective production of interferon (IFN)-γ in response to the vaccine but no spontaneous production, and no induction of anti-Neu IgG3 antibodies. On the other hand, the Triplex cell vaccine induced both Th1 and Th2 cytokines, a strong increase in spontaneous IFN-γ production, and high levels of IgG3 antibodies recognizing Neu-positive syngeneic cells. In conclusion, the Tri-DNA vaccine is as effective as Triplex cell vaccine, exploiting a more restricted immune stimulation.

Original languageEnglish
Pages (from-to)453-464
Number of pages12
JournalHuman Gene Therapy
Volume20
Issue number5
DOIs
Publication statusPublished - May 1 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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