Activity of T Cells Stimulated by Hemagglutinin-neuraminidase of Newcastle Disease Virus in vivo

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To investigate the stimulated activity of T cells and the anti-tumor properties of hemagglutinin-neurami- nidase(HN) of Newcastle disease virus(NDV) strain Changchun(NDVcc), the expression of HN gene in hepatoma ceils(human HepG-2 and mouse H22 cells) infected with the recombinant adenovirus(Ad-HN) was identified by Western blot analysis and flow cytometry. Sialidase activity of NDVcc HN expressed by Ad-HN was assayed by the periodate-resorcinol method. The in vivo anti-tumor effects of NDVcc HN were evaluated in the H22 solid tumor model. Regional lymph nodes of the mouse model treated with Ad-HN were removed to harvest T lymphocytes and evaluating the specific cytotoxicity of cytotoxic T lymphocyte(CTL) and natural killer(NK) cells by an L-lactate de- hydrogenase(LDH) assay, in the mean time, the secretion of cytokines was analyzed by enzyme linked immunosor- bent assays(ELISA). The results show that NDVcc HN was effectively expressed by Ad-HN in HepG-2 and H22 cells. The sialidase activity assay showed that Ad-HN significantly reduced sialic acid level of the hepatoma cells compared with the cells infected the empty adenovirus vector(Ad-mock). When treated with Ad-HN, the growth of subcutane- ous H22 primary tumors in C57BL/6 mice was suppressed, and the mean mice survival increased. In addition, the treatment of Ad-HN elicited strong NK and CTL responses, and high levels of Th 1 cytokines, such as IL-2 and IFN-y. In conclusion, NDVcc HN effectively elicits T cell-mediate anti-tumor cytotoxicity via sialidase activity and may be a novel strategy for cancer immunotherapy.
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