1. Activation of human T cells by a tumor vaccine infected with recombinant Newcastle disease virus producing IL-2.
- Author
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Janke M, Peeters B, Zhao H, de Leeuw O, Moorman R, Arnold A, Ziouta Y, Fournier P, and Schirrmacher V
- Subjects
- Antigens, CD biosynthesis, Antigens, Differentiation, T-Lymphocyte biosynthesis, Carcinoma, Squamous Cell immunology, Carcinoma, Squamous Cell virology, Cell Line, Tumor, Flow Cytometry, Head and Neck Neoplasms immunology, Head and Neck Neoplasms virology, Humans, Lectins, C-Type, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear virology, Lymphocyte Activation, Protein Binding, T-Lymphocytes metabolism, U937 Cells, Cancer Vaccines metabolism, Interleukin-2 metabolism, Newcastle disease virus genetics, T-Lymphocytes virology
- 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 IFNgamma 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 IFNgamma 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.
- Published
- 2008