Immunological prevention of a multigene cancer syndrome

Stefania Croci, Giordano Nicoletti, Lorena Landuzzi, Caria De Giovanni, Annalisa Astolfi, Chiara Marini, Emma Di Carlo, Piero Musiani, Guido Forni, Patrizia Nanni, Pier Luigi Lollini

Research output: Contribution to journalArticlepeer-review

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 -y-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.

Original languageEnglish
Pages (from-to)8428-8434
Number of pages7
JournalCancer Research
Volume64
Issue number22
DOIs
Publication statusPublished - Nov 15 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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