Authors
Yu Huang, Liming Wang, Shan Mei, Fei Zhao, Lingwa Wang, Yu Xie, Zhao Gao, Jiaxun Wang, Ziyue Kong, Yurong He, Yueyue Shi, Wenkai Guo, Bin Ai, Jugao Fang, Fengwen Xu, Fei Guo
Published in
Frontiers in immunology. Volume 17. Pages 1861346. Epub Jul 21, 2026.
Abstract
Oncolytic virotherapy (OVT) represents a promising approach for cancer treatment, employing oncolytic viruses (OVs) that selectively infect and lyse tumor cells while promoting an antitumor immune microenvironment. Vaccinia virus (VACV) serves as an attractive oncolytic vector due to its favorable safety profile, ease of genetic modification, and inherent tumor selectivity.
To enhance both safety and tumor-targeting capability, we constructed a recombinant vaccinia virus, VV-dTF/EE, by deleting the viral J2R and F4L genes and inserting the human neutrophil elastase (ELANE) gene, which exhibits tumor-killing activity. Mechanistic studies evaluated with virus replication selectivity, cell apoptosis, genomic damage, immunogenic cell death, alongside analysis of the immune microenvironment. Efficacy was tested in multiple tumor cell models in vitro and lung cancer models in vivo.
In tumor cell lines and mouse tumor models, VV-dTF/EE demonstrated tumor-restricted replication, potent oncolytic effects, and induction of immunogenic cell death. Furthermore, VV-dTF/EE augmented VACV-induced antitumor immunity by increasing CD8+ T cell infiltration and suppressing M2-like macrophage polarization.
This VV-dTF/EE revealed tumor-selective replication and killing ability while modifying the tumor immune microenvironment to elicit immunogenic cell death. Our findings highlight a novel strategy for safe and effective tumor immunotherapy through dual-gene deletion and ELANE expression in an oncolytic vaccinia platform.
PMID:
42553337
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.
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