Induction of antitumor immunity ex vivo using dendritic cells transduced with fowl pox vector expressing MUC1, CEA, and a triad of costimulatory molecules (rF-PANVAC)

J Immunother. 2012 Sep;35(7):555-69. doi: 10.1097/CJI.0b013e31826a73de.


The fowl pox vector expressing the tumor-associated antigens, mucin-1 and carcinoembryonic antigen in the context of costimulatory molecules (rF-PANVAC) has shown promise as a tumor vaccine. However, vaccine-mediated expansion of suppressor T-cell populations may blunt clinical efficacy. We characterized the cellular immune response induced by ex vivo dendritic cells (DCs) transduced with (rF)-PANVAC. Consistent with the functional characteristics of potent antigen-presenting cells, rF-PANVAC-DCs demonstrated strong expression of mucin-1 and carcinoembryonic antigen and costimulatory molecules, CD80, CD86, and CD83; decreased levels of phosphorylated STAT3, and increased levels of Tyk2, Janus kinase 2, and STAT1. rF-PANVAC-DCs stimulated expansion of tumor antigen-specific T cells with potent cytolytic capacity. However, rF-PANVAC-transduced DCs also induced the concurrent expansion of FOXP3 expressing CD4CD25 regulatory T cells (Tregs) that inhibited T-cell activation. Moreover, Tregs expressed high levels of Th2 cytokines [interleukin (IL)-10, IL-4, IL-5, and IL-13] together with phosphorylated STAT3 and STAT6. In contrast, the vaccine-expanded Treg population expressed high levels of Th1 cytokines IL-2 and interferon-γ and the proinflammatory receptor-related orphan receptor γt (RORγt) and IL-17A suggesting that these cells may share effector functions with conventional TH17 T cells. These data suggest that Tregs expanded by rF-PANVAC-DCs, exhibit immunosuppressive properties potentially mediated by Th2 cytokines, but simultaneous expression of Th1 and Th17-associated factors suggests a high degree of plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4 Antigens / metabolism
  • Cancer Vaccines / genetics
  • Cancer Vaccines / metabolism*
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism*
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / virology
  • Forkhead Transcription Factors / metabolism
  • Fowlpox virus
  • Genetic Vectors
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mucin-1 / genetics
  • Mucin-1 / metabolism*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Th1-Th2 Balance
  • Th17 Cells / immunology*
  • Transduction, Genetic


  • CD4 Antigens
  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • Membrane Glycoproteins
  • Mucin-1
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Panvac-VF
  • STAT Transcription Factors