title: Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer.
abstract: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.
authors: Department of Urology, China Meitan General Hospital, Beijing, China.
authors: T J
authors: TJ
authors: Mai
authors: Department of Urology, China Meitan General Hospital, Beijing, China.
authors: R
authors: R
authors: Ma
authors: Department of Urology, China Meitan General Hospital, Beijing, China.
authors: Z
authors: Z
authors: Li
authors: Department of Urology, China Meitan General Hospital, Beijing, China.
authors: S C
authors: SC
authors: Bi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D010957:Plasmids / Q000235:genetics / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C504399:Psca protein, mouse; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA