Enhanced Anti-Tumor Response Elicited by a Novel Oncolytic Pseudorabies Virus Engineered with a PD-L1 Inhibitor

Autor: Guangtao Xiang, Mengdong Wang, Pu Wang, Rifei Li, Chao Gao, Yue Li, Xinxin Liang, Yun Liu, Aotian Xu, Jun Tang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Viruses, Vol 16, Iss 8, p 1228 (2024)
Druh dokumentu: article
ISSN: 1999-4915
DOI: 10.3390/v16081228
Popis: Oncolytic viruses combined with immunotherapy offer significant potential in tumor therapy. In this study, we engineered a further attenuated pseudorabies virus (PRV) vaccine strain that incorporates a PD-L1 inhibitor and demonstrated its promise as an oncolytic virus in tumor therapy. We first showed that the naturally attenuated PRV vaccine strain Bartha can efficiently infect tumor cells from multiple species, including humans, mice, and dogs in vitro. We then evaluated the safety and anti-tumor efficacy of this vaccine strain and its different single-gene deletion mutants using the B16-F10 melanoma mouse model. The TK deletion strain emerged as the optimal vector, and we inserted a PD-L1 inhibitor (iPD-L1) into it using CRISPR/Cas9 technology. Compared with the control, the recombinant PRV (rPRV-iPD-L1) exhibited more dramatic anti-tumor effects in the B16-F10 melanoma mouse model. Our study suggests that PRV can be developed not only as an oncolytic virus but also a powerful vector for expressing foreign genes to modulate the tumor microenvironment.
Databáze: Directory of Open Access Journals
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