Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine

Carla De Giovanni, Giordano Nicoletti, Lorena Landuzzi, Annalisa Astolfi, Stefania Croci, Alberto Comes, Silvano Ferrini, Raffaella Meazza, Manuela Iezzi, Emma Di Carlo, Piero Musiani, Federica Cavallo, Patrizia Nanni, Pier Luigi Lollini

Research output: Contribution to journalArticlepeer-review

Abstract

This study evaluated the ability of cytokine-engineered allogeneic (H-2q) HER-2/neu-positive cells to prevent tumor development in mammary cancer-prone virgin female BALB/c (H-2d) mice transgenic for the transforming rat HER-2/neu oncogene (BALB-neuT mice). Repeated vaccinations with cells engineered to release interleukin (IL)-2, IL-12, IL-15, or IFN-γ showed that IL-12-engineered cell vaccines had the most powerful immunopreventive activity, with >80% of 1-year-old BALB-neuT mice free of tumors. On the contrary all of the untreated mice and all of the mice vaccinated with IL-12-engineered cells lacking either HER-2/neu or allogeneic antigens developed mammary carcinomas within 22 or 33 weeks, respectively. Whole mount, histology, immunohistochemistry, and gene expression profile analysis showed that vaccination with IL-12-engineered cells maintained 26-week mammary glands free of neoplastic growth, with a gene expression profile that clustered with that of untreated preneoplastic glands. The IL-12-engineered cell vaccine elicited a high production of IFN-γ and IL-4 and a strong anti-HER-2/neu antibody response. Immune protection was lost or markedly impaired in BALB-neuT mice lacking IFN-γ or antibody production, respectively. The protection afforded by the IL-12-engineered cell vaccine was equal to that provided by the systemic administration of recombinant IL-12 in combination with HER-2/neu H-2q cell vaccine. However, IL-12-engineered cell vaccine induced much lower circulating IL-12 and IFN-γ and therefore lower potential side effects and systemic toxicity.

Original languageEnglish
Pages (from-to)4001-4009
Number of pages9
JournalCancer Research
Volume64
Issue number11
DOIs
Publication statusPublished - Jun 1 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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