Published September 20, 2005 | Version v1
Journal article Open

Immunological Prevention of a Multigene Cancer Syndrome

  • 1. 1Cancer Research Section, Department of Experimental Pathology and
  • 2. 1Cancer Research Section, Department of Experimental Pathology and; 2Istituti Ortopedici Rizzoli, Bologna, Italy;
  • 3. 1Cancer Research Section, Department of Experimental Pathology and; 3Interdepartment Center for Cancer Research "Giorgio Prodi," University of Bologna, Bologna, Italy;
  • 4. 4Center of Excellence on Aging (CeSI), "G. D'Annunzio" University, Chieti, Italy; and
  • 5. 5Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

Description

Abstract Vaccines effectively prevent the onset of tumors in transgenic mice carrying activated oncogenes; however, human tumors are caused by combined alterations in oncogenes and oncosuppressor genes. We evaluated the impact of prophylactic vaccines in HER-2/neu transgenic, p53 wild-type/null mice that succumb to an aggressive cancer syndrome comprising mammary and salivary gland carcinomas and rhabdomyosarcoma. A vaccine made of allogeneic mammary carcinoma cells expressing HER-2/neu and interleukin 12 afforded long-term protection from tumor onset. Tumor prevention was mediated by T cell–derived cytokines, in particular γ-interferon, and by anti–HER-2/neu antibodies. HER-2/neu expression was inhibited in target tissues of vaccinated mice, and somatic loss of the wild-type p53 allele did not occur. A highly effective vaccine against a single oncoprotein induced a powerful immune response that arrested multistep carcinogenesis in distinct target tissues.

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