Rescue of nonlytic Newcastle Disease Virus (NDV) expressing IL-15 for cancer immunotherapy

被引:14
作者
Xu, Xiaojing [1 ]
Sun, Qing [2 ,3 ]
Yu, Xiao [1 ]
Zhao, Lixiang [1 ]
机构
[1] Soochow Univ, Med Dept, Coll Basic Med & Biol Sci, Suzhou 215123, Peoples R China
[2] Yangzhou Univ, Coll Vet Med, Lab Anim Infect Dis, Yangzhou 225009, Jiangsu, Peoples R China
[3] Univ Otago, Sch Med, Dept Microbiol & Immunol, Virus Res Unit, Dunedin, New Zealand
基金
中国国家自然科学基金;
关键词
Newcastle disease virus; IL-15; Reverse genetics; Tumor; Vaccine; ANTITUMOR VACCINATION; TUMOR-CELLS; T-CELLS; RECOMBINANT; THERAPY; INTERLEUKIN-2; PROTEIN; VECTOR; GENE; CANDIDATE;
D O I
10.1016/j.virusres.2017.03.003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In order to test and enhance the antitumor activity against mice melanoma by NDV-modified tumor vaccine, a recombinant NDV expressing IL-15 (LX/(IL-15)) was generated by reverse genetics. Then, the expression level and biological activity of IL-15 were examined. Our results showed that mice tumor cell lines infected with LX/(1-15) expressed IL-15 at a high level, and that expressed 1L-15 was biologically active. Expression kinetics demonstrated that the highest expression level of IL-15 was at 48 h post infection. The cytotoxicity assay showed that murine melanoma cells modified with LX/(IL-15) could significantly enhance the antitumor immune response in vitro. In vivo study also showed that murine melanoma cells modified with LX/(IL-15) could prevent melanoma growth in mice. Taken together, our data strongly indicated that recombinant LX/(IL-15)) is a promising agent for cancer immunotherapy both for human and animal. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:35 / 41
页数:7
相关论文
共 27 条
[1]   Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[2]   Engineered Newcastle Disease Virus as an Improved Oncolytic Agent Against Hepatocellular Carcinoma [J].
Altomonte, Jennifer ;
Marozin, Sabrina ;
Schmid, Roland M. ;
Ebert, Oliver .
MOLECULAR THERAPY, 2010, 18 (02) :275-284
[3]   Genetically engineered Newcastle disease virus expressing interleukin 2 is a potential drug candidate for cancer immunotherapy [J].
Bai, Fuliang ;
Niu, Zeshan ;
Tian, Hui ;
Li, Siming ;
Lv, Zheng ;
Zhang, Tianyuan ;
Ren, Guiping ;
Li, Deshan .
IMMUNOLOGY LETTERS, 2014, 159 (1-2) :36-46
[4]   The double-stranded RNA-dependent protein kinase PKR: Structure and function [J].
Clemens, MJ ;
Elia, A .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1997, 17 (09) :503-524
[5]   MTH-68/H oncolytic viral treatment in human high-grade gliomas [J].
Csatary, LK ;
Gosztonyi, G ;
Szeberenyi, J ;
Fabian, Z ;
Liszka, V ;
Bodey, B ;
Csatary, CM .
JOURNAL OF NEURO-ONCOLOGY, 2004, 67 (1-2) :83-93
[6]   IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists [J].
Desbois, Melanie ;
Le Vu, Pauline ;
Coutzac, Clelia ;
Marcheteau, Elie ;
Beal, Coralie ;
Terme, Magali ;
Gey, Alain ;
Morisseau, Sebastien ;
Teppaz, Geraldine ;
Boselli, Lisa ;
Jacques, Yannick ;
Bechard, David ;
Tartour, Eric ;
Cassard, Lydie ;
Chaput, Nathalie .
JOURNAL OF IMMUNOLOGY, 2016, 197 (01) :168-178
[7]   Molecular Programming of Tumor-Infiltrating CD8+ T Cells and IL15 Resistance [J].
Doedens, Andrew L. ;
Rubinstein, Mark P. ;
Gross, Emilie T. ;
Best, J. Adam ;
Craig, David H. ;
Baker, Megan K. ;
Cole, David J. ;
Bui, Jack D. ;
Goldrath, Ananda W. .
CANCER IMMUNOLOGY RESEARCH, 2016, 4 (09) :799-811
[8]   Anticancer Cytokines: Biology and Clinical Effects of Interferon-α2, Interleukin (IL)-2, IL-15, IL-21, and IL-12 [J].
Floros, Theofanis ;
Tarhini, Ahmad A. .
SEMINARS IN ONCOLOGY, 2015, 42 (04) :539-548
[9]   Newcastle disease virus: Current status and our understanding [J].
Ganar, Ketan ;
Das, Moushumee ;
Sinha, Sugandha ;
Kumar, Sachin .
VIRUS RESEARCH, 2014, 184 :71-81
[10]   Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy [J].
Janke, M. ;
Peeters, B. ;
de Leeuw, O. ;
Moorman, R. ;
Arnold, A. ;
Fournier, P. ;
Schirrmacher, V. .
GENE THERAPY, 2007, 14 (23) :1639-1649