title: Enhance the anti-renca carcinoma effect of a DNA vaccine targeting G250 gene by co-expression with cytotoxic T-lymphocyte associated antigen-4(CTLA-4).
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 with a greater affinity. Co-expression specific antigens and extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for its enhancement on G250/MN/CA IX (G250)-specific immune responses and its anti-tumor effects in renal carcinoma mice model. Consequently, we constructed a DNA vaccine containing the G250 and the CTLA-4 gene. Vaccination with the co-expression DNA not only induced much higher level of anti-CTLA4 and anti-G250 antibody, but also increased G250-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with G250-expressing tumors were generated. After injection into the tumor-bearing mouse model, the plasmid carrying the co-expression gene of CTLA4 and G250 showed stronger inhibition of tumor growth than the plasmid expressing CTLA4 or G250 alone. These observations emphasize the potential of the CTLA4 and G250 co-expression DNA vaccine, which could represent a promising approach for tumor immunotherapy.
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China. Electronic address: Zhaoyg717@163.com.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
authors.forename: Qiwu
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China. Electronic address: wangliangcd@hotmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China. Electronic address: lishadan@hotmail.com.
authors.forename: Shadan
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D018390:Gene Targeting / Q000379:methods; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D019444:Vaccines, DNA
keywords: CTLA-4; DNA vaccine; G250; Renal carcinoma