Activation of human T cells by a tumor vaccine infected with recombinant Newcastle disease virus producing IL-2

  • Authors: Markus Janke, Ben Peeters, Heng Zhao, Olav de Leeuw, Rob Moorman, Annette Arnold, Yvonne Ziouta, Philippe Fournier, Volker Schirrmacher
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  • Published online on: Wednesday, October 1, 2008
  • Pages: 823-832
  • DOI: 10.3892/ijo_00000070

Abstract

A new recombinant (rec) Newcastle disease virus (NDV) with incorporated human interleukin 2 (IL-2) as foreign therapeutic gene [rec(IL-2)] will be described. The foreign gene in rec(IL-2) did not affect the main features of NDV replication nor its tumor selectivity. Biologically active IL-2 was produced in high amounts by tumor cells infected with rec(IL-2). Tumor vaccine cells infected by rec(IL-2) stimulated human T cells to exert anti-tumor activity in vitro in a tumor neutralization assay. These effects were significantly increased when compared to vaccine infected by rec(-) virus without IL-2 gene. After incubation with rec(IL-2) infected tumor cells, T cells showed increased expression of the activation marker CD69 and produced increased amounts of IFNγ when compared to T cells co-incubated with rec(-) infected tumor cells. CD8 T cells incubated with rec(IL-2) infected tumor cells showed upregulation of perforin, cell surface exposure of the degranulation marker CD107a and increased anti-tumor cytotoxic activity. Purified T cells from lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients could be stimulated to secrete IFNγ in an ELISPOT assay upon 40 h of stimulation with rec(IL-2) infected autologous tumor cells [ATV-rec(IL-2)] but not upon stimulation with rec(IL-2) infected allogeneic U937 tumor cells. This suggests direct activation of patient derived tumor antigen-specific memory T cells by ATV-rec(IL-2). In conclusion, the already inherent immunostimulatory properties of NDV could be further augmented by the introduction of the therapeutic gene IL-2. Active specific immunization of patients with ATV-rec(IL-2) should provide the microenvironment at the vaccination site with IL-2 and avoid side effects as seen after systemic IL-2 application.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
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APA
Janke, M., Peeters, B., Zhao, H., de Leeuw, O., Moorman, R., Arnold, A., Ziouta, Y., Fournier, P., & Schirrmacher, V. (2008). Activation of human T cells by a tumor vaccine infected with recombinant Newcastle disease virus producing IL-2. International Journal of Oncology, 33(4), 823-832.
MLA
Janke, Peeters, Zhao, de Leeuw, Moorman, Arnold, Ziouta, Fournier, and Volker Schirrmacher. "Activation of human T cells by a tumor vaccine infected with recombinant Newcastle disease virus producing IL-2." International Journal of Oncology International Journal of Oncology 33.4 (2008): 823-832.
Chicago
Janke, Peeters, Zhao, de Leeuw, Moorman, Arnold, Ziouta, Fournier, and Volker Schirrmacher. "Activation of human T cells by a tumor vaccine infected with recombinant Newcastle disease virus producing IL-2." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 823-832.