title: Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine.
abstract: This study evaluated the ability of cytokine-engineered allogeneic (H-2(q)) HER-2/neu-positive cells to prevent tumor development in mammary cancer-prone virgin female BALB/c (H-2(d)) 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-gamma 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-gamma 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-gamma 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-2(q) cell vaccine. However, IL-12-engineered cell vaccine induced much lower circulating IL-12 and IFN-gamma, and therefore lower potential side effects and systemic toxicity.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Bologna. carla.degiovanni@unibo.it
authors.forename: Carla
authors.initials: C
authors.lastname: De Giovanni
authors.forename: Giordano
authors.initials: G
authors.lastname: Nicoletti
authors.forename: Lorena
authors.initials: L
authors.lastname: Landuzzi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.forename: Stefania
authors.initials: S
authors.lastname: Croci
authors.forename: Alberto
authors.initials: A
authors.lastname: Comes
authors.forename: Silvano
authors.initials: S
authors.lastname: Ferrini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Meazza
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
authors.forename: Piero
authors.initials: P
authors.lastname: Musiani
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nanni
authors.forename: Pier-Luigi
authors.initials: PL
authors.lastname: Lollini
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases