This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Giovanni, C. Articles by Lollini, P.-L. Search for Related Content PubMed PubMed Citation Articles by De Giovanni, C. Articles by Lollini, P.-L.

Immunoprevention of HER-2/neu Transgenic Mammary Carcinoma through an Interleukin 12-Engineered Allogeneic Cell Vaccine

¹ Cancer Research Section, Department of Experimental Pathology, University of Bologna, Bologna; ² Istituti Ortopedici Rizzoli, Bologna; ³ Istituto Nazionale per la Ricerca sul cancro, IST, Genoa; ⁴ Istituto Scientifico G. Gaslini, Genoa; ⁵ Aging Research Centre, "G. D’Annunzio" University Foundation, Chieti; and ⁶ Department of Clinical and Biological Sciences, University of Turin, Ospedale S. Luigi Gonzaga, Orbassano, Italy

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- 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- 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- 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-, and therefore lower potential side effects and systemic toxicity.

This article has been cited by other articles:

				L. Menotti, A. Cerretani, H. Hengel, and G. Campadelli-Fiume Construction of a Fully Retargeted Herpes Simplex Virus 1 Recombinant Capable of Entering Cells Solely via Human Epidermal Growth Factor Receptor 2 J. Virol., October 15, 2008; 82(20): 10153 - 10161. [Abstract] [Full Text] [PDF]

				P. Nanni, G. Nicoletti, A. Palladini, S. Croci, A. Murgo, A. Antognoli, L. Landuzzi, M. Fabbi, S. Ferrini, P. Musiani, et al. Antimetastatic Activity of a Preventive Cancer Vaccine Cancer Res., November 15, 2007; 67(22): 11037 - 11044. [Abstract] [Full Text] [PDF]

				F. Pappalardo, P.-L. Lollini, F. Castiglione, and S. Motta Modeling and simulation of cancer immunoprevention vaccine Bioinformatics, June 15, 2005; 21(12): 2891 - 2897. [Abstract] [Full Text] [PDF]

				A. Astolfi, L. Landuzzi, G. Nicoletti, C. De Giovanni, S. Croci, A. Palladini, S. Ferrini, M. Iezzi, P. Musiani, F. Cavallo, et al. Gene Expression Analysis of Immune-Mediated Arrest of Tumorigenesis in a Transgenic Mouse Model of HER-2/neu-Positive Basal-Like Mammary Carcinoma Am. J. Pathol., April 1, 2005; 166(4): 1205 - 1216. [Abstract] [Full Text] [PDF]

				M. Croce, R. Meazza, A. M. Orengo, L. Radic', B. De Giovanni, C. Gambini, B. Carlini, V. Pistoia, L. Mortara, R. S. Accolla, et al. Sequential Immunogene Therapy with Interleukin-12- and Interleukin-15-Engineered Neuroblastoma Cells Cures Metastatic Disease in Syngeneic Mice Clin. Cancer Res., January 15, 2005; 11(2): 735 - 742. [Abstract] [Full Text] [PDF]

				S. Croci, G. Nicoletti, L. Landuzzi, C. De Giovanni, A. Astolfi, C. Marini, E. Di Carlo, P. Musiani, G. Forni, P. Nanni, et al. Immunological Prevention of a Multigene Cancer Syndrome Cancer Res., November 15, 2004; 64(22): 8428 - 8434. [Abstract] [Full Text] [PDF]