Anti-tumor Immunity of Newcastle Disease Virus HN Protein is Influenced by Differential Subcellular Targeting

• Main Authors: Kaibing WANG, Hong SUI, Lejing LI, Xi LI, Lei WANG
• Format: Article
• Language: zho
• Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2010-08-01
• Series: Chinese Journal of Lung Cancer
• Subjects: Hemagglutinin-neuraminidase (HN) protein; Cellular localization; Anti-tumor immunity; Cytotoxic T lymphocyte
• Online Access: http://www.lungca.org/index.php?journal=01&page=article&op=viewFile&path[]=10.3779%2Fj.issn.1009-3419.2010.08.04&path[]=1642

Background and objective Hemagglutinin-neuraminidase (HN) protein of newcastle disease virus is an important immunogen for oncolysis. We designed three different expression plasmids encoding the HN protein targeted to different subcellular compartments: cytoplasmic (Cy-HN), secreted (Sc-HN) and membrane-anchored (M-HN). On the basis of antitumor effect in vitro, the aim of this study is to investigate the anti-tumor immunity effect of HN protein in vivo. Methods In the present study, we developed a mouse model in order to evaluate the anti-tumor effect of the intratumorally injected modified HN proteins and the anti-tumor immunity by lymphocyte proliferative response and CTL activity test. Results Although all three DNA constructs elicited an immune response, tumor-bearing mice intratumorally injected with M-HN demonstrated a significantly better anti-tumor effect than those injected with Cy-HN or Sc-HN (Day 18: P=0.022; Day 21: P < 0.01). It also showed that this anti-tumor effect was mediated by higher lymphocyte proliferative response and CTL activity in mice intratumorally injected with M-HN [M-HN vs Cy-HN, P=0.019; M-HN vs Sc-HN, P=0.043; M-HN vs pcDNA3.1(+), P < 0.01]. Conclusion The anti-tumor immunity of Newcastle disease virus HN protein is influenced by differential subcellular targeting. The membrane-anchored form of the HN protein appears to be an ideal candidate to improve the specific cellular immunity.