Abstract
Prostate cancer (PCa) is the most commonly diagnosed type of cancer in men in western industrialized countries. As a public health burden, the need for the invention of new cost-saving PCa immunotherapies is apparent. In this study, we present a DNA vaccine encoding for the prostate-specific antigen prostatic acid phosphatase (PAP) linked to the J-domain and the SV40 enhancer sequence. The PAP DNA vaccine induced a strong PAP-specific cellular immune response after electroporation (EP)-based delivery in C57BL/6 mice. Splenocytes from mice immunized with PAP recognized the naturally processed PAP epitopes, indicating that vaccination with the PAP-J gene broke its self-tolerance against PAP. Remarkably, DNA vaccination with PAP-J inhibited tumor growth in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model that closely resembled human PCa. Therefore, this study highlights a novel cancer immunotherapy approach with the potential to control PCa in clinical settings.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acid Phosphatase
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Antibodies / immunology
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology
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Cell Line
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Disease Models, Animal
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Disease Progression
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Epitopes / immunology
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Epitopes / metabolism
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Genetic Vectors / genetics
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H-2 Antigens / immunology
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H-2 Antigens / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Peptides / immunology
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Peptides / metabolism
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / immunology
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Prostatic Neoplasms / therapy*
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Protein Binding
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / genetics*
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Protein Tyrosine Phosphatases / immunology
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Self Tolerance / genetics*
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T-Lymphocytes, Cytotoxic / immunology
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Vaccines, DNA / immunology
Substances
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Antibodies
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Antigens, Neoplasm
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Cancer Vaccines
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Epitopes
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H-2 Antigens
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Peptides
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Vaccines, DNA
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Acid Phosphatase
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prostatic acid phosphatase
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Protein Tyrosine Phosphatases