Transcriptional IL-15-directed in vivo DC targeting DNA vaccine.
Dendritic cells (DC) engineered in vitro by DNA encoding OVAhsp70 and IL-15 up-regulated their expressions of CD80, CD86, CCR7 and IL-15Ralpha and promoted their productions of IL-6, IL-12 and TNF-alpha. Transcriptional IL-15-directed in vivo DC targeting DNA vaccine encoding OVAhsp70 elicited long-lasting Th1 and CTL responses and anti-B16OVA activity. CD8T cell-mediated primary tumor protection was abrogated by DC or CD4T cell depletion during the induction phase of immune responses. However, CD4T cell depletion during immunization did not impair CD8T cell-dependent long-lasting tumor protection. Furthermore, in vivo DC-derived IL-15 exerted the enhancements of cellular and humoral immune responses and antitumor immunity elicited by OVAhsp70 DNA vaccine. Importantly, the potency of this novel DNA vaccine strategy was proven using a self/tumor Ag (TRP2) in a clinically relevant B16 melanoma model. These findings have implications for developing next generation DNA vaccines against cancers and infectious diseases in both healthy and CD4 deficient individuals.
Tian
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Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Liu
Z
Z
Donahue
C
C
Noh
H S
HS
Falo
L D
LD
You
Z
Z
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics* / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014158:Transcription, Genetic; D019444:Vaccines, DNA / Q000276:immunology*
D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D019409:Interleukin-15; D019444:Vaccines, DNA; D010047:Ovalbumin