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 journalArticle

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

Fingerprint

DNA Vaccines
Vaccines
Neoplasms
Interleukin-12
Major Histocompatibility Complex
Interferons
Immunoglobulin G
Alleles
erbB-2 Genes
Gene Components
Th1 Cells
Cancer Vaccines
Antibodies
Transgenes
Genes
Anti-Idiotypic Antibodies
Immunization
Plasmids
Breast Neoplasms
Cytokines

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

De Giovanni, C., Nicoletti, G., Palladini, A., Croci, S., Landuzzi, L., Antognoli, A., ... Lollini, P. L. (2009). A multi-DNA preventive vaccine for p53/neu-driven cancer syndrome. Human Gene Therapy, 20(5), 453-464. https://doi.org/10.1089/hum.2008.172

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 journalArticle

De Giovanni, C, Nicoletti, G, Palladini, A, Croci, S, Landuzzi, L, Antognoli, A, Murgo, A, Astolfi, A, Ferrini, S, Fabbi, M, Orengo, AM, Amici, A, Penichet, ML, Aurisicchio, L, Iezzi, M, Musiani, P, Nanni, P & Lollini, PL 2009, 'A multi-DNA preventive vaccine for p53/neu-driven cancer syndrome', Human Gene Therapy, vol. 20, no. 5, pp. 453-464. https://doi.org/10.1089/hum.2008.172
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. / A multi-DNA preventive vaccine for p53/neu-driven cancer syndrome. In: Human Gene Therapy. 2009 ; Vol. 20, No. 5. pp. 453-464.
@article{a72c138e880c4eeb837cec1a686947c5,
title = "A multi-DNA preventive vaccine for p53/neu-driven cancer syndrome",
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.",
author = "{De Giovanni}, C. and G. Nicoletti and A. Palladini and S. Croci and L. Landuzzi and A. Antognoli and A. Murgo and A. Astolfi and S. Ferrini and M. Fabbi and Orengo, {A. M.} and A. Amici and Penichet, {M. L.} and L. Aurisicchio and M. Iezzi and P. Musiani and P. Nanni and Lollini, {P. L.}",
year = "2009",
month = "5",
day = "1",
doi = "10.1089/hum.2008.172",
language = "English",
volume = "20",
pages = "453--464",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

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 -