Enhanced Oncolytic Potential of Engineered Newcastle Disease Virus Lasota Strain through Modification of Its F Protein Cleavage Site

被引:0
|
作者
Li, Zedian [1 ]
Qian, Weifeng [1 ]
Zhang, Yuhao [1 ]
Liao, Chengshui [1 ]
Chen, Jian [1 ]
Ding, Ke [1 ]
Yu, Qingzhong [2 ]
Jia, Yanyan [1 ]
He, Lei [1 ,2 ]
机构
[1] Henan Univ Sci & Technol, Key Lab Anim Dis & Publ Hlth, Luoyang Key Lab Live Carrier Biomat & Anim Dis Pre, Luoyang 471023, Peoples R China
[2] ARS, Southeast Poultry Res Lab, US Natl Poultry Res Ctr, USDA, Athens, GA 30605 USA
关键词
Newcastle disease virus; fusion protein cleavage site; oncolytic effect; murine melanoma; VECTOR; NDV;
D O I
10.3390/microorganisms12102029
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Newcastle disease virus (NDV) is an oncolytic virus whose F protein cleavage activity is associated with viral infectivity. To explore the potential of modifying F protein cleavage activity to enhance antitumor effects, we constructed a recombinant NDV LaSota strain by replacing its F protein cleavage site with that from the mesogenic Beaudette C (BC) strain using reverse genetics techniques. The resulting virus, rLaSota-BC-RFP, demonstrated significantly enhanced infectivity and tumor cell suppression on the murine melanoma B16F10 cell, characterized by higher cytotoxicity and increased apoptosis compared to its parental strain, rLaSota-RFP. In vivo, rLaSota-BC-RFP treatment of B16F10 tumors in C57BL/6 mice resulted in significant tumor growth inhibition, improved survival rate, and induction of tumor-specific apoptosis and necrosis. Additionally, the rLaSota-BC-RFP treatment enhanced immunostimulatory effects within the tumor microenvironment (TME), characterized by increased infiltration of CD4+ and CD8+ T cells and elevated levels of antitumor immune modulator cytokines, including mouse IL-12, IFN-gamma, IL-15, and TNF-alpha, in the rLaSota-BC-RFP-treated tumor tissues. Collectively, these findings demonstrate that the mesogenic F protein cleavage site enhances the oncolytic potential of the NDV LaSota strain, suggesting that rLaSota-BC-RFP is a promising oncolytic viral vector for gene delivery in cancer immunotherapy.
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页数:15
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