Abstract
We describe the use of retrogen plasmid-based vaccine technology to break tolerance and to generate a robust, dose-dependent antibody response against the self cancer antigen, survivin. We further demonstrate that this phenomenon is due to the incorporation of the survivin antigen into the retrogen system rather than to some peculiarity unique to survivin. In contrast to other genetic immunization methods designed to produce antibody responses, the retrogen system results in a broad range of antibody isotypes, indicative of both a Th-1 and a Th-2 CD4+ response. Additional evidence of a Th-1 response is demonstrated by tumor growth inhibition in a mouse model of colon cancer metastasis. We speculate that this cost-effective technology could one day bolster or even supplant the use of monoclonal antibodies in the targeting of cell surface cancer antigens.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies / blood*
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Antigens, Neoplasm / biosynthesis
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Cancer Vaccines / administration & dosage*
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Cancer Vaccines / immunology
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Colorectal Neoplasms / blood
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Colorectal Neoplasms / immunology
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Colorectal Neoplasms / prevention & control*
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Dose-Response Relationship, Immunologic
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Female
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Inhibitor of Apoptosis Proteins
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Mice
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Mice, Inbred BALB C
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Microtubule-Associated Proteins / biosynthesis
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / immunology
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Neoplasm Transplantation
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Repressor Proteins
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Survivin
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Th1 Cells / immunology
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Th2 Cells / immunology
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Vaccination / methods
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / immunology
Substances
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Antibodies
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Antigens, Neoplasm
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Birc5 protein, mouse
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Cancer Vaccines
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins
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Repressor Proteins
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Survivin
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Vaccines, DNA