DNA vaccine with α-galactosylceramide at prime phase enhances anti-tumor immunity after boosting with antigen-expressing dendritic cells.
DNA vaccines contribute to a promising new approach for the generation of cytotoxic T lymphocytes (CTL). DNA vaccines do have several disadvantages, including poor immunogenicity and oncogene expression. We used the natural killer T-cell (NKT) ligand α-galactosylceramide (α-GalCer) as an adjuvant to prime initial DNA vaccination; and used the potent immune-stimulatory tumor antigen-expressing dendritic cells (DCs) as a booster vaccination. A DNA vaccine expressing human papillomavirus (HPV) type 16 E7 (pcDNA3-CRT/E7) was combined with α-GalCer at the prime phase, and generated a higher number of E7-specific CD8(+) T-cells in vaccinated mice than vaccine used at boost phase. Therefore, priming with a DNA vaccine in the presence of α-GalCer and boosting with E7-pulsed DC-1 led to a significant enhancement of E7-specific CD8(+) effector and memory T-cells as well as significantly improved therapeutic and preventive effects against an E7-expressing tumor model (TC-1) in vaccinated mice. Our findings suggested that the potency of a DNA vaccine combined with α-GalCer could be further enhanced by boosting with an antigen-expressing DC-based vaccine to generate anti-tumor immunity.
Kim
Daejin
D
Department of Anatomy, Chung-Ang University, College of Medicine, Seoul, Republic of Korea. kimdj@cau.ac.kr
Hung
Chien-Fu
CF
Wu
T-C
TC
Park
Yeong-Min
YM
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage* / Q000276:immunology; D007117:Immunization, Secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D005699:Galactosylceramides; D050725:Papillomavirus E7 Proteins; D019444:Vaccines, DNA; C493154:alpha-galactosylceramide; C059731:oncogene protein E7, Human papillomavirus type 16
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