The anti-tumor effect of Newcastle disease virus HN protein is influenced by differential subcellular targeting.
BACKGROUND
Immunotherapy is emerging as a major player in the current standard of care for aggressive cancers such as non-small cell lung cancer (NSCLC). The Newcastle disease virus with its tumor-specific replicative and oncolytic abilities is a promising immunotherapeutic candidate. A DNA vaccine expressing the major immunogenic hemagglutinin-neuraminidase (HN) protein of this virus has shown promising results as an immunotherapeutic agent.


METHODS
In the present study, three different DNA vaccine constructs encoding differentially targeted HN proteins (cytoplasmic or Cy-HN, secreted or Sc-HN and membrane-anchored or M-HN) were generated to evaluate their anti-tumor effect in vitro and in vivo.


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. We also showed that this anti-tumor effect was mediated by higher lymphocyte proliferative response and CTL activity in mice intratumorally injected with M-HN.


CONCLUSIONS
The membrane-anchored form of the HN protein appears to be an ideal candidate to develop as an immunotherapeutic agent for NSCLC.
Medical Department, The Tumor Hospital Affiliated Harbin Medical University, Harbin, Heilongjiang, China.
Hong
H
Sui
Yuxian
Y
Bai
Kaibing
K
Wang
Xi
X
Li
Chun
C
Song
Fang
F
Fu
Yongxin
Y
Zhang
Lejing
L
Li
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D015707:HN Protein / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D009522:Newcastle disease virus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines; D015707:HN Protein; D019444:Vaccines, DNA