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The anti-tumor effect of Newcastle disease virus HN protein is influenced by differential subcellular targeting

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

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.

Conclusion

The membrane-anchored form of the HN protein appears to be an ideal candidate to develop as an immunotherapeutic agent for NSCLC.

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Authors and Affiliations

  1. Medical Department, The Tumor Hospital Affiliated Harbin Medical University, Harbin, 150040, Heilongjiang, China

    Hong Sui, Yuxian Bai & Lejing Li

  2. Interventional Department, The Second Hospital Affiliated Harbin Medical University, Harbin, Heilongjiang, China

    Kaibing Wang

  3. Division of Swine Disease, National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Medicine, Harbin, Heilongjiang, China

    Xi Li, Fang Fu & Yongxin Zhang

  4. The Key Laboratory of Cell Transplantation of Ministry of Health, The First Hospital Affiliated Harbin Medical University, Harbin, Heilongjiang, China

    Chun Song

Authors
  1. Hong Sui
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  2. Yuxian Bai
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  3. Kaibing Wang
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  4. Xi Li
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  5. Chun Song
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  6. Fang Fu
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  7. Yongxin Zhang
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  8. Lejing Li
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Corresponding author

Correspondence to Lejing Li.

Additional information

H. Sui, Y. Bai and X. Li contributed equally to this work.

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Sui, H., Bai, Y., Wang, K. et al. The anti-tumor effect of Newcastle disease virus HN protein is influenced by differential subcellular targeting. Cancer Immunol Immunother 59, 989–999 (2010). https://doi.org/10.1007/s00262-010-0821-5

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  • DOI: https://doi.org/10.1007/s00262-010-0821-5

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