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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Endemic Poultry Viral Diseases Research » Research » Publications at this Location » Publication #413615
Research Project: Systems Biology Approaches to Develop Medical Countermeasures to Detect, Prevent, and Control Poultry Production Viral Diseases

Location: Endemic Poultry Viral Diseases Research

Title: Enhanced oncolytic effect of engineered Newcastle disease virus Lasota strain in the B16-F10 murine melanoma model

Author
item LI, ZEDIAN - Henan University Of Science And Technology
item JIA, YANYAN - Henan University Of Science And Technology
item QIAN, WEIFENG - Henan University Of Science And Technology
item LIAO, CHENGSHUI - Henan University Of Science And Technology
item CHEN, JIAN - Henan University Of Science And Technology
item DING, KE - Henan University Of Science And Technology
item Yu, Qingzhong
item HE, LEI - Henan University Of Science And Technology

Submitted to: Microorganisms
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/2/2024
Publication Date: 10/8/2024
Citation: Li, Z., Jia, Y., Qian, W., Liao, C., Chen, J., Ding, K., Yu, Q., He, L. 2024. Enhanced oncolytic effect of engineered Newcastle disease virus Lasota strain in the B16-F10 murine melanoma model. Microorganisms. 12(10). https://doi.org/10.3390/.
DOI: https://doi.org/10.3390/microorganisms12102029

Interpretive Summary: Newcastle disease virus (NDV), an avian pathogen, can preferentially replicate in cancer cells and depress tumor formation but does not harm normal human cells. NDV fusion (F) protein cleavage activity has been proven to correlate with viral infectivity and virulence in poultry. However, it is unclear whether changing the fusion protein cleavage activity of NDV could benefit its anti-tumoral effect. In the present study, we engineered an NDV LaSota vaccine strain-based recombinant virus with a potential F protein cleavage activity increase. We evaluated the LaSota recombinant's anti-cancer effects on the mouse's black tumor cell models. The data showed that the NDV LaSota recombinant induced more damage in the black tumor cells than its parental virus. The treatment of the black tumor in mice with the recombinant virus significantly inhibited tumor growth with a higher mouse survival rate than its parental virus and control. These results proved that increasing the F protein cleavage activity of the NDV LaSota strain could enhance its infectivity and anti-tumor activity, suggesting the LaSota recombinant is a promising candidate for cancer immunotherapy.

Technical Abstract: Newcastle disease virus (NDV) is an oncolytic virus, and its fusion protein cleavage activity has been proven to correlate with viral infectivity. However, it is unclear whether changing the fusion protein cleavage activity could benefit its antitumoral effect. In the present study, using reverse genetics technology, we generated an NDV LaSota vaccine strain-based recombinant virus by replacing its F protein cleavage site with that of the mesogenic Beaudette C strain (BC) to increase the F cleavage ability. The oncolytic abilities of the NDV recombinant, rLaSota-BC-RFP, and its parental virus, rLaSota-RFP, were compared on the murine melanoma B16F10 cell models in vitro and in vivo. In the B16F10 cells, the rLaSota-BC-RFP virus notably increased infectivity and suppressed the tumor cells’ proliferation with higher cytotoxicity and more severe apoptosis than its parental virus. Injection/treatment of the implanted B16F10 tumors in C57BL/6 mice with the rLaSota-BC-RFP virus resulted in tumor-specific apoptosis and necrosis. The rLaSota-BC-RFP virus significantly inhibited tumor growth with a higher survival rate than its parental virus. A significant increase in CD4+ and CD8+ T cell infiltration and the antitumor immune modulator cytokines, such as mouse IL-12, IFN-', IL-15, IL-18, and TNF-a, was also detected in the rLaSota-BC-RFP treated tumor tissues. Together, these results demonstrated that the mesogenic F protein cleavage site enhanced the NDV LaSota strain infectivity and antitumor activity, suggesting the rLaSota-BC-RFP virus is a promising reagent for cancer immunotherapy.