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*
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy;
Biology Molecular, Cellular and Animal, University of Camerino, Camerino, Italy;
Department of Oncology and Neuroscience, G. d’Annunzio University, Chieti, Italy;
§
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy;
¶
Institute for Cancer Research, University of Bologna, Bologna, Italy; and
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Division of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy
The ability of vaccination with plasmids coding for the extracellular and the transmembrane domain of the product of transforming rat Her-2/neu oncogene (r-p185) to protect against r-p185+ transplantable carcinoma (TUBO) cells and mammary carcinogenesis was evaluated. In normal BALB/c mice, DNA vaccination elicits anti-r-p185 Ab, but only a marginal CTL reactivity, and protects against a TUBO cell challenge. Massive reactive infiltration is associated with TUBO cell rejection. In BALB/c mice transgenic for the rat Her-2/neu gene (BALB-neuT), DNA vaccination elicits a lower anti-r-p185 Ab response, no CTL activity and only incompletely protects against TUBO cells, but markedly hampers the progression of carcinogenesis. At 33 wk of age, when control BALB-neuT mice display palpable tumors in all mammary glands, about 60% of immunized mice are tumor free, and tumor multiplicity is markedly reduced. Tumor-free mammary glands still display the atypical hyperplasia of the early stages of carcinogenesis, and a marked down-modulation of r-p185, along with a massive reactive infiltrate. However, BALB-neuT mice protected against mammary carcinogenesis fail to efficiently reject a TUBO cell challenge. This suggests that the mechanisms required for the rejection of transplantable tumors may not coincide with those that inhibit the slow progression of carcinogenesis.
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P. Cappello, F. Triebel, M. Iezzi, C. Caorsi, E. Quaglino, P.-L. Lollini, A. Amici, E. Di Carlo, P. Musiani, M. Giovarelli, et al. LAG-3 Enables DNA Vaccination to Persistently Prevent Mammary Carcinogenesis in HER-2/neu Transgenic BALB/c Mice Cancer Res., May 15, 2003; 63(10): 2518 - 2525. [Abstract] [Full Text] [PDF]
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