Transcriptional IL-15-directed in vivo DC targeting DNA vaccine

• Published in: Gene therapy Vol. 16; no. 10; pp. 1260 - 1270
• Main Authors: Tian, S, Liu, Z, Donahue, C, Noh, H S, Falo, L D, You, Z
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2009; Nature Publishing Group
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antitumor activity; Applied cell therapy and gene therapy; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer vaccines; Cancer Vaccines - immunology; CCR7 protein; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD80 antigen; CD86 antigen; Cell Biology; Cells; Cytotoxicity; Cytotoxicity, Immunologic - immunology; Dendritic cells; Dendritic Cells - immunology; Deoxyribonucleic acid; DNA; DNA vaccines; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Therapy; Genetic aspects; Genetic transcription; Health aspects; Health. Pharmaceutical industry; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - immunology; Human Genetics; Immune response (humoral); Immune system; Immunization; Industrial applications and implications. Economical aspects; Infectious diseases; Interleukin 12; Interleukin 15; Interleukin 6; Interleukin-15 - genetics; Interleukin-15 - immunology; Lymphocytes T; Medical sciences; Melanoma; Melanoma, Experimental - immunology; Melanoma, Experimental - prevention & control; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Molecular genetics; Nanotechnology; original-article; Ovalbumin - genetics; Ovalbumin - immunology; Physiological aspects; Skin cancer; T-Lymphocytes, Cytotoxic - immunology; Th1 Cells - immunology; Transcription; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tumor necrosis factor-α; Tumors; Vaccines; Vaccines, DNA - immunology; United States; DNA vaccine; IL-15; DC targeting; antitumor immunity; Antineoplastic agent; In vivo; Targeting; Transcription; Interleukin 15; Gene therapy; Genetic vaccine; Immunity
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2009.110

Dendritic cells (DC) engineered
in vitro
by DNA encoding OVAhsp70 and IL-15 up-regulated their expressions of CD80, CD86, CCR7 and IL-15Rα and promoted their productions of IL-6, IL-12 and TNF-α. 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.