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Cancer Immunology, Immunotherapy

, Volume 50, Issue 8, pp 397–407 | Cite as

Transduction of human dendritic cells with a recombinant modified vaccinia Ankara virus encoding MUC1 and IL-2

  • Katrina T. Trevor
  • Evan M. Hersh
  • Jacquie Brailey
  • Jean-Marc Balloul
  • Bruce Acres
Original Article

Abstract.

The epithelial mucin MUC1 is considered an opportune target antigen for cancer immunotherapy, as it is over-expressed and exhibits aberrant glycosylation in malignant cells. Because dendritic cells (DC) are powerful initiators of immune responses, efforts have focused on tumor antigen-bearing DC as potent cancer vaccines. In this study we have characterized the transduction of monocyte-derived DC with a highly attenuated vaccinia virus vector [modified vaccinia Ankara (MVA)] encoding human MUC1 and the immunostimulatory cytokine IL-2. Analysis of transduced DC cultures generated from a number of donors revealed MUC1 expression in the range of 27–54% of the cells and a co-regulated secretion of bioactive IL-2. As shown by FACS analysis with MUC1-specific antibodies, the MVA-MUC1/IL-2-transduced DC predominantly expressed the fully processed glycoform of MUC1, typical of that displayed by normal epithelia. Over a 3-day period after transduction, transgene expression declined concurrent with an increase in MVA-induced cytopathic effects. The transduced DC stimulated allogeneic lymphocyte proliferation, indicating that DC immunostimulatory function is not impaired by vector transduction. In the presence of IL-2, MVA-transduced DC were able to enhance autologous lymphocyte proliferation. Also, vector expression was analyzed in DC cultures treated with TNF-α, a known DC maturation factor. As indicated by the up-regulation of several DC maturation markers, neither virus infection nor transgene expression influenced the maturation capacity of the cells. The MVA-MUC1/IL-2 vector effectively transduced both immature and TNF-α-matured DC. Overall, our results are encouraging for the clinical application of MVA-MUC1/IL-2-transduced DC.

Dendritic cells Modified vaccinia Ankara MUC1 Immunotherapy IL-2 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Katrina T. Trevor
    • 1
  • Evan M. Hersh
    • 1
  • Jacquie Brailey
    • 1
  • Jean-Marc Balloul
    • 2
  • Bruce Acres
    • 2
  1. 1.Arizona Cancer Center, 1515 N. Campbell Av., Tucson, AZ 85724, USA
  2. 2.Transgene S.A., Strasbourg, France

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