Combined Allogeneic Tumor Cell Vaccination and Systemic Interleukin 12 Prevents Mammary Carcinogenesis in HER-2/neu Transgenic Mice

• DOI: 10.1084/jem.194.9.1195
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Patrizia Nanni; Giordano Nicoletti; Carla De Giovanni; Lorena Landuzzi; Emma Di Carlo; Federica Cavallo; Serenella M. Pupa; Ilaria Rossi; Mario P. Colombo; Cinzia Ricci; Annalisa Astolfi; Piero Musiani; Guido Forni; Pier-Luigi Lollini
• Keywords: CD4-Positive T-Lymphocytes; Mice, Knockout; Immunity, Cellular; Mice, Inbred BALB C; Cell Transplantation; Receptor, ErbB-2; Vaccination; Mammary Neoplasms, Experimental; Mice, Transgenic; Cancer Vaccines; Interleukin-12; Rats; 3. Good health; Interferon-gamma; Mice; 03 medical and health sciences; 0302 clinical medicine; Adjuvants, Immunologic; Tumor Cells, Cultured; Animals; Transplantation, Homologous; Female; Breast

Transgenic Balb/c mice expressing the transforming rat HER-2/neu oncogene develop early and multifocal mammary carcinomas. Within first 5 months of life tissue-specific expression causes a progression in all their 10 glands from atypical hyperplasia to invasive carcinoma. It was previously observed that chronic administration interleukin (IL)-12 increased tumor latency, but every mouse eventually succumbed multiple A significant improvement prevention sought by administering allogeneic carcinoma cells combined with systemic IL-12. This treatment reduced incidence 90% more than doubled lifetime. For maximum p185neu antigen must be expressed cells. IL-12 strongly cell vaccine efficacy. The receiving displayed markedly epithelial proliferation, angiogenesis, expression, while few hyperplastic foci were heavily infiltrated granulocytes, macrophages, CD8+ lymphocytes. Specific anti–HER-2/neu antibodies produced nonpolarized activation CD4+ secreting IL-4 interferon (IFN)-γ evident. central role for IFN-γ preventive effect proven lack efficacy vaccination gene knockout transgenic mice. possible requirement is related its on antibody production, particular IgG2a IgG2b subclasses, not induced In conclusion, our data show an HER-2/neu–expressing can prevent onset genetically determined tumors.