The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2d) mice carrying the activated HER-2/ neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2q) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8+ T lymphocyte–depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.
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3 August 1998
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August 03 1998
Interleukin 12–mediated Prevention of Spontaneous Mammary Adenocarcinomas in Two Lines of Her-2/neu Transgenic Mice
Katia Boggio,
Katia Boggio
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Giordano Nicoletti,
Giordano Nicoletti
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Emma Di Carlo,
Emma Di Carlo
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Federica Cavallo,
Federica Cavallo
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Lorena Landuzzi,
Lorena Landuzzi
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Cecilia Melani,
Cecilia Melani
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Mirella Giovarelli,
Mirella Giovarelli
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Ilaria Rossi,
Ilaria Rossi
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Patrizia Nanni,
Patrizia Nanni
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Carla De Giovanni,
Carla De Giovanni
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Page Bouchard,
Page Bouchard
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Stanley Wolf,
Stanley Wolf
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Andrea Modesti,
Andrea Modesti
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Piero Musiani,
Piero Musiani
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Pier Luigi Lollini,
Pier Luigi Lollini
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Mario P. Colombo,
Mario P. Colombo
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Guido Forni
Guido Forni
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
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Katia Boggio
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Giordano Nicoletti
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Emma Di Carlo
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Federica Cavallo
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Lorena Landuzzi
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Cecilia Melani
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Mirella Giovarelli
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Ilaria Rossi
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Patrizia Nanni
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Carla De Giovanni
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Page Bouchard
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Stanley Wolf
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Andrea Modesti
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Piero Musiani
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Pier Luigi Lollini
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Mario P. Colombo
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Guido Forni
From the *Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy; the ‡Institute for Cancer Research, University of Bologna, 40126 Bologna, Italy; the §IST Biotechnology Satellite Unit of Bologna, 40126 Bologna, Italy; the ‖Department of Oncology and Neuroscience, G. d'Annunzio University, 66013 Chieti, Italy; the ¶National Tumor Institute, 20133 Milan, Italy; and the **Genetics Institute, Cambridge, Massachusetts 02140
Address correspondence to Guido Forni, Dipartimento di Scienze Cliniche e Biologiche, Universitá di Torino, Ospedale San Luigi Gonzaga, 10043 Orbassano, Italy. Phone: 39-11-9038-638; Fax: 39-11-9038-639; E-mail: [email protected]
This work is dedicated to the memory of Giorgio Prodi, M.D., Ph.D., ten years after his untimely death.
Received:
April 01 1998
Revision Received:
May 11 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (3): 589–596.
Article history
Received:
April 01 1998
Revision Received:
May 11 1998
Citation
Katia Boggio, Giordano Nicoletti, Emma Di Carlo, Federica Cavallo, Lorena Landuzzi, Cecilia Melani, Mirella Giovarelli, Ilaria Rossi, Patrizia Nanni, Carla De Giovanni, Page Bouchard, Stanley Wolf, Andrea Modesti, Piero Musiani, Pier Luigi Lollini, Mario P. Colombo, Guido Forni; Interleukin 12–mediated Prevention of Spontaneous Mammary Adenocarcinomas in Two Lines of Her-2/neu Transgenic Mice . J Exp Med 3 August 1998; 188 (3): 589–596. doi: https://doi.org/10.1084/jem.188.3.589
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