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Xenogeneic immunization in mice using HER2 DNA delivered by an adenoviral vector.

Abstract
The protective efficacy of xenogeneic vaccination with DNA encoding the HER2 oncogene was evaluated in BALB/c mice transgenic for the transforming form of the neu oncogene, which spontaneously develops carcinomas in all mammary glands. Intramuscular injection of either plasmid DNA followed by electrical stimulation (pVIJ-HER2 with ES) or an adenoviral vector (Ad5-HER2), both expressing the HER2 oncogene, was tested. Immunization using pVIJ-HER2 with ES elicited a cell-mediated response that was much lower than that elicited by the immunization with Ad5-HER2, as measured by the frequency of IFN-gamma-secreting spleen cells. The dominant T-cell epitope of the HER2 protein product (p185) in the BALB/c (H-2(d)) genetic background was identified. While the T-cell response elicited was only partially crossreactive with the corresponding rat epitopes because of sequence variations (89% similarity), a cytotoxic T-lymphocyte activity against the rat immunodominant epitope was also evident. The Ad5-HER2 vaccination induced also antibodies against p185, which crossreacted with the rat protein homolog. Both T- and B-cell responses slowly declined with time. Vaccination with Ad5-HER2 at 6 and 9 weeks of age delayed incidence and reduced multiplicity of tumors in neu transgenic mice.
AuthorsPasquale Gallo, Sridhar Dharmapuri, Maurizio Nuzzo, Daniele Maldini, Manuela Iezzi, Federica Cavallo, Piero Musiani, Guido Forni, Paolo Monaci
JournalInternational journal of cancer (Int J Cancer) Vol. 113 Issue 1 Pg. 67-77 (Jan 01 2005) ISSN: 0020-7136 [Print] United States
PMID15386429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Heterophile
  • Cancer Vaccines
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Vaccines, DNA
  • Interferon-gamma
  • Receptor, ErbB-2
Topics
  • Adenoviridae (genetics, immunology)
  • Animals
  • Antibodies, Heterophile (immunology)
  • Cancer Vaccines (administration & dosage, genetics, immunology)
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Female
  • Flow Cytometry
  • Genes, erbB-2 (immunology)
  • Genetic Vectors (genetics, immunology)
  • Immunodominant Epitopes
  • Interferon-gamma
  • Mammary Neoplasms, Experimental (immunology, prevention & control)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Plasmids (genetics, immunology)
  • Rats
  • Receptor, ErbB-2 (genetics, immunology)
  • T-Lymphocytes, Cytotoxic (immunology)
  • Vaccines, DNA (administration & dosage, genetics, immunology)

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