Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / immunology
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Adenocarcinoma / pathology
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Adenocarcinoma / prevention & control
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Animals
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / immunology*
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Antineoplastic Agents / therapeutic use
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Carcinoma, Lobular / genetics
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Carcinoma, Lobular / immunology
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Carcinoma, Lobular / pathology
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Carcinoma, Lobular / prevention & control*
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / immunology*
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Cell Transformation, Neoplastic / pathology
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Female
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Genetic Predisposition to Disease
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / immunology
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Mammary Neoplasms, Experimental / pathology
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Mammary Neoplasms, Experimental / prevention & control*
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Neoplasm Transplantation / immunology*
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Neoplasm Transplantation / pathology
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Rats
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Receptor, ErbB-2 / genetics*
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Receptor, ErbB-2 / immunology*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / immunology
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Tumor Cells, Cultured / transplantation
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology
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Vaccines, DNA / therapeutic use*
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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Recombinant Proteins
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Vaccines, DNA
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Receptor, ErbB-2