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

Gene Therapy volume 16, pages 1260–1270 (2009)Cite this article

Abstract

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.

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Acknowledgements

We are indebted to TA Waldmann (NIH), T Brocker (Ludwig-Maximilians-Universitat Munchen), G Erdos (University of Pittsburgh) and E Lord and J Frelinger (University of Rochester) for providing reagents. We are also indebted to RM Steinman (The Rockefeller University) for his constructive help. This work was supported by NIH grant R01CA108813 (to ZY), R01 AI076060, CA106662, and P01 CA73743 (to LDF).

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Authors and Affiliations

  1. Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    S Tian, Z Liu, C Donahue, H S Noh, L D Falo Jr & Z You

  2. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    L D Falo Jr & Z You

  3. Departments of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Z You

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Correspondence to Z You.

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Tian, S., Liu, Z., Donahue, C. et al. Transcriptional IL-15-directed in vivo DC targeting DNA vaccine. Gene Ther 16, 1260–1270 (2009). https://doi.org/10.1038/gt.2009.110

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