Nat Commun: Injection of synthetic RNA viruses to treat cancer and address the limitations of oncolytic viruses

Oncolytic viruses (OV) have become a very attractive form of cancer treatment, oncolytic viruses target cancer cells without affecting normal cells, by replicating within cancer cells, leading to cancer cell lysis, while oncolytic viruses can also activate the tumor microenvironment (TME

Combining oncolytic viruses with cancer immunotherapy has the potential to further reshape the tumor microenvironment (TME) and immune cell activation, enhancing the efficacy

As of now, the treatment of oncolytic virus is limited to injection to the tumor site, requiring a systemic anti-tumor response to be effective

To maximize the potential of viral immunotherapy, strategies must be developed to avoid neutralization of antibodies in the human body

On October 7, 2022, researchers published a research paper

The research team has developed a completely synthetic RNA virus, Synthetic RNA virus, which delivers the RNA viral genome (vRNA) through lipid nanoparticles (LNP), which will solve the limitations of repeated intravenous administration of oncolytic viruses and improve the therapeutic potential

This synthetic virus is well tolerated and has been shown in a variety of tumor models to selectively kill tumor cells after intravenous injection, leading to tumor lysis and antitumor efficacy

For this study, the team selected two viruses – Seneca Valley virus (SVV) and Coxsackievirus A21 (CVA21), which have good oncolytic activity and clinical safety

The results show that this synthetic virus is well tolerated and demonstrated in a variety of tumor models that it can selectively kill tumor cells after intravenous injection, resulting in tumor lysis and antitumor efficacy, and can also enhance the antitumor household type

Oncorus has two main lines of research and development: modified herpes simplex virus and synthetic virus

In the case of modified oncolytic viruses, there are two therapies under study, both using herpes simplex virus (HSV), ONCR-177 (for the treatment of melanoma, head and neck squamous cell carcinoma, and triple-negative breast cancer), and ONCR-GBM (for the treatment of central nervous system cancers such as glioma), which is in Phase 1 clinical trials

In terms of synthetic viruses, there are two therapies under research, both using lipid nanoparticles (LNP) to deliver RNA viral genome (vRNA), namely ONCR-021, ONCR-788, the former encoding optimized coxsackievirus A21 (CVA21), for the treatment of non-small cell lung cancer, hepatocellular carcinoma, clear cell renal cell carcinoma, melanoma,

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