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 language | English |
|---|---|
| Pages (from-to) | 453-464 |
| Number of pages | 12 |
| Journal | Human Gene Therapy |
| Volume | 20 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2009 |
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ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
Cite this
A multi-DNA preventive vaccine for p53/neu-driven cancer syndrome. / De Giovanni, C.; Nicoletti, G.; Palladini, A.; Croci, S.; Landuzzi, L.; Antognoli, A.; Murgo, A.; Astolfi, A.; Ferrini, S.; Fabbi, M.; Orengo, A. M.; Amici, A.; Penichet, M. L.; Aurisicchio, L.; Iezzi, M.; Musiani, P.; Nanni, P.; Lollini, P. L.
In: Human Gene Therapy, Vol. 20, No. 5, 01.05.2009, p. 453-464.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A multi-DNA preventive vaccine for p53/neu-driven cancer syndrome
AU - De Giovanni, C.
AU - Nicoletti, G.
AU - Palladini, A.
AU - Croci, S.
AU - Landuzzi, L.
AU - Antognoli, A.
AU - Murgo, A.
AU - Astolfi, A.
AU - Ferrini, S.
AU - Fabbi, M.
AU - Orengo, A. M.
AU - Amici, A.
AU - Penichet, M. L.
AU - Aurisicchio, L.
AU - Iezzi, M.
AU - Musiani, P.
AU - Nanni, P.
AU - Lollini, P. L.
PY - 2009/5/1
Y1 - 2009/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=66149115499&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66149115499&partnerID=8YFLogxK
U2 - 10.1089/hum.2008.172
DO - 10.1089/hum.2008.172
M3 - Article
C2 - 19215191
AN - SCOPUS:66149115499
VL - 20
SP - 453
EP - 464
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 5
ER -