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)

Baldev Vasir, Corrine Zarwan, Rehan Ahmad, Keith D. Crawford, Hassan Rajabi, Ken-ichi Matsuoka, Jacalyn Rosenblatt, Zekui Wu, Heidi Mills, Donald Kufe, David Avigan

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)555-569
Number of pages15
JournalJournal of Immunotherapy
Volume35
Issue number7
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

Fingerprint

Fowlpox
Dendritic Cells
Immunity
T-Lymphocytes
Mucin-1
Carcinoembryonic Antigen
Neoplasm Antigens
Cytokines
Vaccines
Janus Kinase 2
Interferon Receptors
Th17 Cells
Cancer Vaccines
Interleukin-13
Interleukin-17
Interleukin-5
Antigen-Presenting Cells
Regulatory T-Lymphocytes
Immunosuppressive Agents
Cellular Immunity

Keywords

  • Listeria
  • myelopoiesis
  • tumor microenvironment
  • tumor progression
  • tumor-associated macrophages

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology

Cite this

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). / Vasir, Baldev; Zarwan, Corrine; Ahmad, Rehan; Crawford, Keith D.; Rajabi, Hassan; Matsuoka, Ken-ichi; Rosenblatt, Jacalyn; Wu, Zekui; Mills, Heidi; Kufe, Donald; Avigan, David.

In: Journal of Immunotherapy, Vol. 35, No. 7, 09.2012, p. 555-569.

Research output: Contribution to journalArticle

Vasir, Baldev ; Zarwan, Corrine ; Ahmad, Rehan ; Crawford, Keith D. ; Rajabi, Hassan ; Matsuoka, Ken-ichi ; Rosenblatt, Jacalyn ; Wu, Zekui ; Mills, Heidi ; Kufe, Donald ; Avigan, David. / 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). In: Journal of Immunotherapy. 2012 ; Vol. 35, No. 7. pp. 555-569.
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AU - Zarwan, Corrine

AU - Ahmad, Rehan

AU - Crawford, Keith D.

AU - Rajabi, Hassan

AU - Matsuoka, Ken-ichi

AU - Rosenblatt, Jacalyn

AU - Wu, Zekui

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AU - Kufe, Donald

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