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

M. Janke, B. Peeters, H. Zhao, O. Leeuw, R.J.M. Moormann, A. Arnold, Y. Ziouta, P. Fournier, V. Schirrmacher

    Research output: Contribution to journalArticleAcademicpeer-review

    28 Citations (Scopus)

    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 IFN gamma 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 perform, 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 IFN gamma 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.
    Original languageEnglish
    Pages (from-to)823-832
    JournalInternational Journal of Oncology
    Volume33
    Issue number4
    DOIs
    Publication statusPublished - 2008

    Keywords

    • antitumor vaccination
    • fusion protein
    • bone-marrow
    • therapy
    • cancer
    • memory
    • immunotherapy
    • parameters
    • carcinoma

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