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

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)397-407
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume50
Issue number8
DOIs
StatePublished - 2001

Fingerprint

Vaccinia virus
Dendritic Cells
Interleukin-2
Vaccinia
Transgenes
Cell Culture Techniques
Lymphocytes
Cancer Vaccines
Neoplasm Antigens
Mucins
Virus Diseases
Glycosylation
Immunotherapy
Monocytes
Up-Regulation
Epithelium

Keywords

  • Dendritic cells
  • IL-2
  • Immunotherapy
  • Modified vaccinia Ankara
  • MUC1

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Transduction of human dendritic cells with a recombinant modified vaccinia Ankara virus encoding MUC1 and IL-2. / Trevor, Katrina T.; Hersh, Evan M; Brailey, Jacquie; Balloul, Jean Marc; Acres, Bruce.

In: Cancer Immunology, Immunotherapy, Vol. 50, No. 8, 2001, p. 397-407.

Research output: Contribution to journalArticle

Trevor, Katrina T. ; Hersh, Evan M ; Brailey, Jacquie ; Balloul, Jean Marc ; Acres, Bruce. / Transduction of human dendritic cells with a recombinant modified vaccinia Ankara virus encoding MUC1 and IL-2. In: Cancer Immunology, Immunotherapy. 2001 ; Vol. 50, No. 8. pp. 397-407.
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