Identification of in vitro and in vivo oncolytic effect in colorectal cancer cells by Orf virus strain NA1/11

Abstract

Orf virus (ORFV) is a favorable oncolytic viral carrier in research, and ORFV strain NZ2 has been revealed to have antitumor effects in animal models mediated by immunoregulation profile. However, the antitumor effects triggered by the ORFV in colorectal cancer (CRC) cells is poorly characterized. The in vivo and in vitro roles of ORFV in CRC were determined using western blotting, colony formation, CCK-8, wound scratch assay, qPCR, and animal models. Furthermore, cytokine antibody chip assay, flow cytometry, western blotting, and immunohistochemical (IHC) assays were conducted to explore the potential mechanism of ORFV. The present data revealed that ORFV strain NA1/11 infected and inhibited the in vitro growth and migration of CRC cells. By establishing a CRC model in Balb/c mice, it was revealed that ORFV strain NA1/11 significantly inhibited the in vivo growth and migration of CRC cells. A cytokine antibody array was utilized to obtain a more comprehensive profile revealing the differentially expressed cytokines in ORFV infection. Cytokines, such as IL-7, IL-13, IL-15, CD27, CD30, pentraxin 3, and B lymphocyte chemoattractant (BLC), were upregulated. Axl, CXCL16, ANG-3, MMP10, IFN-γ R1 and VEGF-B were downregulated. The results indicated that ORFV played roles in the regulation of key factors relevant to apoptosis, autoimmunity/inflammation, angiogenesis, and the cell cycle. Finally, data was presented to validate that ORFV infection induces oncolytic activity by enhancing apoptosis in vivo and in vitro . In conclusion, ORFV could be an oncolytic virus for CRC therapy.

Coxsackievirus Group B3 Has Oncolytic Activity against Colon Cancer through Gasdermin E-Mediated Pyroptosis

“…After the virus infects cells, it immediately induces robust death, and there are no oncogenes associated with the virus that might cause secondary tumorigenesis. The abnormal replication of tumor cells and the enrichment of some receptors on their surface create a microenvironment favoring viral replication that makes CVB3 better able to infect these hyperactive cells, causing apoptosis, pyroptosis, necrosis, or cell cycle arrest [ 33 , 34 , 35 ].…”

Oncolytic viruses combined with immune checkpoint therapy for colorectal cancer is a promising treatment option

“…Orf virus (ORFV) can rapidly mediate innate and adaptive immune responses in vivo, so it has been proposed as a potential oncolytic virus vector. Studies have demonstrated that ORFV strain NA1/11 can inhibit CRC growth and metastasis by inducing apoptosis in CRC cells (27). In addition, a research team (28) produced M51R genetically engineered recombinant virus from cDNA clones containing the M protein mutation to construct M51R vesicular stomatitis virus (M51R VSV), which inhibits CRC peritoneal surface spread (PSD).…”

Oncolytic Viruses: Immunotherapy Drugs for Gastrointestinal Malignant Tumors

“…Oncolytic viruses are usually natural or modified viruses that target and kill tumor cells. These viruses regulate key intracellular processes and anti-viral responses such as apoptosis, inflammation, angiogenesis, and the cell cycle (Chen et al, 2021). Also, oncolytic viruses can enhance the host's anti-tumor immunity through multiple mechanisms (Ramelyte et al, 2021).…”