Xenogeneic immunization in mice using HER2 DNA delivered by an adenoviral vector.
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.
Gallo
Pasquale
P
Molecular and Cell Biology Department, Istituto di Ricerche di Biologia Melecolare P. Angeletti, Pomezia, Italy.
Dharmapuri
Sridhar
S
Nuzzo
Maurizio
M
Maldini
Daniele
D
Iezzi
Manuela
M
Cavallo
Federica
F
Musiani
Piero
P
Forni
Guido
G
Monaci
Paolo
P
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D005434:Flow Cytometry; D018734:Genes, erbB-2 / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D016056:Immunodominant Epitopes; D007371:Interferon-gamma; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000910:Antibodies, Heterophile; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA