期刊
INTERNATIONAL JOURNAL OF CANCER
卷 113, 期 1, 页码 67-77出版社
WILEY
DOI: 10.1002/ijc.20536
关键词
antitumor vaccination; breast cancer; adenovirus; neu transgenic mice
类别
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 Ad5HER2 at 6 and 9 weeks of age delayed incidence and reduced multiplicity of tumors in neu transgenic mice. (C) 2004 Wiley-Liss, Inc.
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