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    Keywords: CANCER ; CELLS ; EXPRESSION ; IN-VITRO ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; Germany ; human ; THERAPY ; VITRO ; DISEASE ; EXPOSURE ; SITE ; GENE ; PATIENT ; ACTIVATION ; IFN-GAMMA ; MARKER ; LYMPH-NODES ; T cell ; T cells ; T-CELL ; T-CELLS ; BONE-MARROW ; MEMORY ; STIMULATION ; virus ; ASSAY ; PARAMETERS ; HEAD ; VACCINE ; REPLICATION ; squamous cell carcinoma ; ELISPOT ; IMMUNOTHERAPY ; vaccination ; side effects ; IL-2 ; FUSION PROTEIN ; INTERLEUKIN-2 ; INCREASED EXPRESSION ; CELL CARCINOMA ; FEATURES ; ONCOLOGY ; RECOMBINANT ; NODES ; RE ; HNSCC ; NEWCASTLE-DISEASE-VIRUS ; Newcastle disease virus ; lymph nodes ; ANTITUMOR VACCINATION ; SQUAMOUS-CELL ; systemic ; DEGRANULATION ; cancer vaccination ; CYTOTOXIC ACTIVITY ; tumor therapy ; anti-tumor activity ; anti-tumor ; interleukin 2
    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
    Type of Publication: Journal article published
    PubMed ID: 18813797
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