title: Enhancement of DNA vaccine potency through coadministration of CIITA DNA with DNA vaccines via gene gun.
abstract: Administration of DNA vaccines via gene gun has emerged as an important form of Ag-specific immunotherapy. The MHC CIITA is a master regulator of MHC class II expression and also induces expression of class I molecules. We reasoned that the gene gun administration of CIITA DNA with DNA vaccines employing different strategies to improve MHC I and II processing could enhance DNA vaccine potency. We observed that DC-1 cells transfected with CIITA DNA lead to higher expression of MHC I and II molecules, leading to enhanced Ag presentation through the MHC I/II pathways. Furthermore, our data suggested that coadministration of DNA-encoding calreticulin (CRT) linked to human papillomavirus (HPV) 16 E6 Ag (CRT/E6) with CIITA DNA leads to enhanced E6-specific CD8(+) T cell immune responses in vaccinated mice. In addition, coadministration of the combination of CRT/E6 DNA with CIITA DNA and DNA encoding the invariant chain (Ii) linked to the pan HLA-DR-reactive epitope (Ii-PADRE) further enhanced E6-specific CD8(+) T cell immune responses in vaccinated mice. Treatment with the combination vaccine was also shown to enhance the antitumor effects and to prolong survival in TC-1 tumor-bearing mice. Vaccination with the combination vaccine also led to enhanced E6-specific CD8(+) memory T cells and to long-term protection against TC-1 tumors and prolonged survival in vaccinated mice. Thus, our findings suggest that the combination of CIITA DNA with CRT/E6 and Ii-PADRE DNA vaccines represents a potentially effective means to combat tumors in the clinical setting.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.forename: Talia
authors.initials: T
authors.lastname: Hoory
authors.forename: Archana
authors.initials: A
authors.lastname: Monie
authors.forename: Jenny Pan-Yun
authors.initials: JP
authors.lastname: Ting
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D019470:Biolistics / Q000379:methods*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D037282:Calreticulin / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000517:prevention & control; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D037282:Calreticulin; D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D017780:Malaria Vaccines; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; C401223:PADRE 45; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16