[新城疫病毒HN蛋白的抗肿瘤免疫受亚细胞靶向差异的影响]

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

作者信息

Wang Kaibing, Sui Hong, Li Lejing, Li Xi, Wang Lei

机构信息

Interventional Department, the Second Hospital Affiliated to Harbin Medical University, Harbin 150086, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2010 Aug;13(8):773-6. doi: 10.3779/j.issn.1009-3419.2010.08.04.

DOI:10.3779/j.issn.1009-3419.2010.08.04

PMID:20704816

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6000555/

Abstract

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.

摘要

背景与目的

新城疫病毒的血凝素 - 神经氨酸酶（HN）蛋白是一种重要的溶瘤免疫原。我们设计了三种不同的表达质粒，它们编码靶向不同亚细胞区室的HN蛋白：细胞质（Cy - HN）、分泌型（Sc - HN）和膜锚定型（M - HN）。基于体外抗肿瘤作用，本研究旨在探讨HN蛋白在体内的抗肿瘤免疫效果。

方法

在本研究中，我们建立了一个小鼠模型，以通过淋巴细胞增殖反应和CTL活性测试来评估瘤内注射修饰后的HN蛋白的抗肿瘤效果及抗肿瘤免疫力。

结果

尽管所有三种DNA构建体均引发了免疫反应，但瘤内注射M - HN的荷瘤小鼠显示出比注射Cy - HN或Sc - HN的小鼠显著更好的抗肿瘤效果（第18天：P = 0.022；第21天：P < 0.01）。这也表明，这种抗肿瘤效果是由瘤内注射M - HN的小鼠中更高的淋巴细胞增殖反应和CTL活性介导的[M - HN与Cy - HN比较，P = 0.019；M - HN与Sc - HN比较，P = 0.043；M - HN与pcDNA3.1(+)比较，P < 0.01]。