title: Anti-tumor effects of DNA vaccine targeting human fibroblast activation protein α by producing specific immune responses and altering tumor microenvironment in the 4T1 murine breast cancer model.
abstract: Fibroblast activation protein α (FAPα) is a tumor stromal antigen overexpressed by cancer-associated fibroblasts (CAFs). CAFs are genetically more stable compared with the tumor cells and immunosuppressive components of the tumor microenvironment, rendering them excellent targets for cancer immunotherapy. DNA vaccines are widely applied due to their safety. To specifically destroy CAFs, we constructed and examined the immunogenicity and anti-tumor immune mechanism of a DNA vaccine expressing human FAPα. This vaccine successfully reduced 4T1 tumor growth through producing FAPα-specific cytotoxic T lymphocyte responses which could kill CAFs, and the decrease in FAPα-expressing CAFs resulted in markedly attenuated expression of collagen I and other stromal factors that benefit the tumor progression. Based on these results, a DNA vaccine targeting human FAPα may be an attractive and effective cancer immunotherapy strategy.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Xia
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Geng
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Chen-Lu
authors.initials: CL
authors.lastname: Liu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Lu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China. Zhanghh@jlu.edu.cn.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun, 130012, People's Republic of China.
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Yu
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000276:immunology / Q000378:metabolism; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018093:Gelatinases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D019496:Cancer Vaccines; D024042:Collagen Type I; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D019444:Vaccines, DNA; D000099167:Fibroblast Activation Protein Alpha
keywords: CAF; DNA vaccine; FAPα; Immune suppression; Immunotherapy