Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine - PubMed (original) (raw)

. 2004 Jun 1;64(11):4001-9.

doi: 10.1158/0008-5472.CAN-03-2984.

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

Affiliations

• PMID: 15173014
• DOI: 10.1158/0008-5472.CAN-03-2984

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

Carla De Giovanni et al. Cancer Res. 2004.

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.

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