Attenuated WNV-poly(A) exerts a broad-spectrum oncolytic effect by selective virus replication and CD8+ T cell-dependent immune response - 13/01/23
Abstract |
As an emerging tumor therapy, ideal oncolytic viruses preferentially replicate in malignant cells, reverse the immunosuppressive tumor microenvironment, and eventually can be eliminated by the patient. It is of great significance for cancer treatment to discover new excellent oncolytic viruses. Here, we found that WNV live attenuated vaccine WNV-poly(A) could be developed as a novel ideal oncolytic agent against several types of cancers. Mechanistically, due to its high sensitivity to type Ι interferon (IFN-Ι), WNV-poly(A) could specifically kill tumor cells rather than normal cells. At the same time, WNV-poly(A) could activate Dendritic cells (DCs) and trigger tumor antigen specific response mediated by CD8 + T cell, which contributed to inhibit the propagation of original and distal tumor cells. Like intratumoral injection, intravenous injection with WNV-poly(A) also markedly delays Huh7 hepatic carcinoma (HCC) transplanted tumor progression. Most importantly, in addition to an array of mouse xenograft tumor models, WNV-poly(A) also has a significant inhibitory effect on many different types of patient-derived tumor tissues and HCC patient-derived xenograft (PDX) tumor models. Our studies reveal that WNV-poly(A) is a potent and excellent oncolytic agent against many types of tumors and may have a role in metastatic and recurrent tumors.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | WNV-poly(A) is a potent and excellent oncolytic agent, which exerts a broad-spectrum oncolytic effect against several types of cancers. |
• | Due to its high sensitivity to IFN-I, WNV-poly(A) selectively infected and killed tumor cells, but not normal cells. |
• | WNV-poly(A) treatment triggered CD8+ T cell mediated anti-tumor immune response. |
• | WNV-poly(A) has significant therapeutic effects on a variety of patient-derived tumor tissues. |
Abbreviations : IFN-Ι, DCs, Hpi, i.v., LAV, i.m., WNV, i.p., FBS, HCC, CCK8, ABSL-2, moi, FACS, PDX, dpi, HDST, IF, PI, TUNEL
Keywords : WNV-poly(A), Oncolytic virus, IFN-I-dependent selectivity, CD8+ T cell, Immunity therapy, Broad spectrum
Plan
Vol 158
Article 114094- février 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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