[Anti-tumor immunity of Newcastle disease virus HN protein is influenced by differential subcellular targeting].
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].


CONCLUSIONS
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.
Wang
Kaibing
K
Interventional Department, the Second Hospital Affiliated to Harbin Medical University, Harbin 150086, China.
Sui
Hong
H
Li
Lejing
L
Li
Xi
X
Wang
Lei
L
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D015707:HN Protein / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000970:Antineoplastic Agents; D015707:HN Protein; D014764:Viral Proteins