title: An artificial PAP gene breaks self-tolerance and promotes tumor regression in the TRAMP model for prostate carcinoma.
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.
authors.affiliation: Division of Immunology, Department of Biology, University of Constance, Constance, Germany. elmar.spies@uni-konstanz.de
authors.forename: Elmar
authors.initials: E
authors.lastname: Spies
authors.forename: Wilfried
authors.initials: W
authors.lastname: Reichardt
authors.forename: Gerardo
authors.initials: G
authors.lastname: Alvarez
authors.forename: Marcus
authors.initials: M
authors.lastname: Groettrup
authors.forename: Peter
authors.initials: P
authors.lastname: Ohlschläger
mesh_terms: D000135:Acid Phosphatase; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D017634:Self Tolerance / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D006183:H-2 Antigens; D010455:Peptides; D019444:Vaccines, DNA; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases
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