DNA Vaccination Against Rat Her-2/Neu p185 More Effectively Inhibits Carcinogenesis Than Transplantable Carcinomas in Transgenic BALB/c Mice

The ability of vaccination with plasmids coding for the extracellular and the transmembrane domain of the product of transforming rat Her-2/neu oncogene (r-p185) to protect against r-p185(+) transplantable carcinoma (TUBO) cells and mammary carcinogenesis was evaluated. In normal BALB/c mice, DNA va...

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Published in:The Journal of immunology (1950) 2000-11, Vol.165 (9), p.5133-5142
Main Authors: Rovero, Stefania, Amici, Augusto, Carlo, Emma Di, Bei, Roberto, Nanni, Patrizia, Quaglino, Elena, Porcedda, Paola, Boggio, Katia, Smorlesi, Arianna, Lollini, Pier-Luigi, Landuzzi, Lorena, Colombo, Mario P, Giovarelli, Mirella, Musiani, Piero, Forni, Guido
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - immunology
Adenocarcinoma - pathology
Adenocarcinoma - prevention & control
Animals
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - immunology
Antineoplastic Agents - therapeutic use
cancer vaccines
Carcinoma, Lobular - genetics
Carcinoma, Lobular - immunology
Carcinoma, Lobular - pathology
Carcinoma, Lobular - prevention & control
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - immunology
Cell Transformation, Neoplastic - pathology
Female
Genetic Predisposition to Disease
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - immunology
Mammary Neoplasms, Experimental - pathology
Mammary Neoplasms, Experimental - prevention & control
Mice
Mice, Inbred BALB C
Mice, Transgenic
Neoplasm Transplantation - immunology
Neoplasm Transplantation - pathology
Rats
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - immunology
Recombinant Proteins - biosynthesis
Recombinant Proteins - immunology
Tumor Cells, Cultured - transplantation
Vaccines, DNA - administration & dosage
Vaccines, DNA - immunology
Vaccines, DNA - therapeutic use
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Summary:The ability of vaccination with plasmids coding for the extracellular and the transmembrane domain of the product of transforming rat Her-2/neu oncogene (r-p185) to protect against r-p185(+) transplantable carcinoma (TUBO) cells and mammary carcinogenesis was evaluated. In normal BALB/c mice, DNA vaccination elicits anti-r-p185 Ab, but only a marginal CTL reactivity, and protects against a TUBO cell challenge. Massive reactive infiltration is associated with TUBO cell rejection. In BALB/c mice transgenic for the rat Her-2/neu gene (BALB-neuT), DNA vaccination elicits a lower anti-r-p185 Ab response, no CTL activity and only incompletely protects against TUBO cells, but markedly hampers the progression of carcinogenesis. At 33 wk of age, when control BALB-neuT mice display palpable tumors in all mammary glands, about 60% of immunized mice are tumor free, and tumor multiplicity is markedly reduced. Tumor-free mammary glands still display the atypical hyperplasia of the early stages of carcinogenesis, and a marked down-modulation of r-p185, along with a massive reactive infiltrate. However, BALB-neuT mice protected against mammary carcinogenesis fail to efficiently reject a TUBO cell challenge. This suggests that the mechanisms required for the rejection of transplantable tumors may not coincide with those that inhibit the slow progression of carcinogenesis.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.165.9.5133