title: Specific antitumor immune response induced by a novel DNA vaccine composed of multiple CTL and T helper cell epitopes of prostate cancer associated antigens.
abstract: The loss of immunogenic epitopes by tumors has urged the development of vaccines against multiple epitopes. Recombinant DNA technologies have opened the possibility to develop multiepitope vaccines in a relatively rapid and efficient way. In this study, several DNA fragments encoding multiple cytotoxic T lymphocyte (CTL) and T helper (Th) cell epitopes were selected from human prostate-specific membrane antigen (hPSM), mouse prostatic acid phosphatase (mPAP), and human prostate-specific antigen (hPSA), These DNA fragments were ligated together to form a novel fusion gene, termed 3P gene. The 3P gene and human IgG Fc gene were inserted into pcDNA3.1 to construct a DNA vaccine designated psig-3P-Fc. Vaccination with psig-3P-Fc by gene gun inoculation induced strong antitumor response in a mouse tumor model, which significantly inhibited tumor growth and prolonged survival time of the tumor-bearing mice. In vitro, when lymphocytes were stimulated by psig-3P-Fc-transfected autologous peripheral blood mononuclear cells (PBMC), CTLs were induced which could specifically kill hPSM-, hPAP-, or hPSA-expressing tumor cells. These observations provide a new vaccine strategy for cancer therapy through concomitant enhancement of antigen specific CD4(+) helper and CD8(+) cytotoxic T-cell responses against tumors.
authors.affiliation: Department of Immunology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, 17 Pan Jia Yuan Nan Li, Chao Yang District, Beijing 100021, China.
authors.forename: Hanjun
authors.initials: H
authors.lastname: Qin
authors.forename: Chunxia
authors.initials: C
authors.lastname: Zhou
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Wenbo
authors.initials: W
authors.lastname: Ma
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.forename: Youhui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shuren
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D019444:Vaccines, DNA; D004247:DNA