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The Journal of Immunology, 2006, 176: 7695-7703.
Copyright © 2006 by The American Association of Immunologists

Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent of HER-2/neu Expression1

Tania Pannellini*,{dagger}, Michela Spadaro{ddagger}, Emma Di Carlo*,{dagger}, Elena Ambrosino{ddagger}, Manuela Iezzi*,{dagger}, Augusto Amici§, Pier Luigi Lollini, Guido Forni{ddagger}, Federica Cavallo2,3,{ddagger} and Piero Musiani2,*,{dagger}

* Aging Research Center, CeSi, G. d’Annunzio University Foundation, Chieti, Italy; {dagger} Department of Oncology and Neurosciences, "G. D’Annunzio" University, Chieti, Italy; {ddagger} Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy; § Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy; and Cancer Research Section, Department of Experimental Pathology, University of Bologna, Bologna, Italy

Double transgenic mice overexpressing the transforming rat HER-2/neu oncogene and the mutated p53, with both dominant-negative and a gain-of-function properties, display early aggressive and metastasizing parotid tumors. Multiple acinar and ductal hyperplasia foci overexpressing the HER-2/neu gene product are evident at wk 5 and progress to poorly differentiated carcinoma by wk 7. Mice die before wk 18 with invasive carcinomas and multiple metastases that no longer express HER-2/neu. A combination of repeated electroporations of plasmids coding for the extracellular and transmembrane domains of the rat HER-2/neu receptor with systemic IL-12 administrations started when the parotids that present diffuse hyperplasia protected all female and 50% of the male mice until the close of the experiment at wk 40. This combined treatment began when multifocal in situ carcinomas that were already present cured 33% of the females and 25% of the males. The most prominent immunologic features associated with the antitumor protection were the production of high titers of anti-HER-2/neu Abs and the nonappearance of cell-mediated cytotoxic reactivity. In conclusion, anti-HER-2/neu vaccination combined with systemic IL-12 control parotid carcinomas as far as p53 mutation makes their growth independent of HER-2/neu expression.




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