Novel chemotactic-antigen DNA vaccine against cancer.
Dendritic cells play a pivotal role in immune induction. Dendritic cells perform antigen uptake, processing and presentation to T cells only when they are matured and in the functional state. In the development of a vaccine, it is of utmost importance to consider how to make dendritic cells' functions immunologically adequate. In this paper, we report the development of a series of antitumor DNA vaccines with similar structural framework, in which a gene encoding tumor-associated antigenic peptide is ligated upstream to the gene coding secondary lymphoid-tissue chemokine and downstream to the gene encoding the Fc portion of IgG (named chemotactic-antigen DNA vaccine [CADV]). CCR7(+) T, B, natural killer and dendritic cells can be attracted by secondary lymphoid-tissue chemokine, and Fc facilitates antigen uptake via Fc receptors expressed on dendritic cells. In a series of experiments in mice vaccinated by CADV with such tumor-associated antigenic specificities as HPV-16 E7, PSA-PSM-PAP, HER-2/neu, p53 and hTERT, CADV can attract immune cells to the vaccine inoculation site, remarkably inhibit tumor growth and extend survival time in tumor-bearing mice. The antitumor effect is more efficacious than that in mice treated with SLC-Ag or Ag-Fc hybrid gene. Tumor-associated antigenic-specific cytotoxic T lymphocytes can be induced by in vitro experiment in a human system. When combined with measures blocking the negative immune feedback circuits, the therapeutic effect of the vaccine can be further enhanced. Large-scale production of CADV is possible for clinical application.
Zhang
Shuren
S
Peking Union Medical College, Department of Immunology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing 100021, China. biotherapy@caca.sina.net
Zhang
Youhui
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018925:Chemokines / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018925:Chemokines; D007141:Immunoglobulin Fc Fragments; D019444:Vaccines, DNA