Synthetic RNA viruses are injected to treat cancer and address the limitations of oncolytic viruses

Written by Wang Cong
Editor Wang Duoyu typesetting Water Chengwen

Oncolytic viruses (OV) has become a very attractive cancer treatment method, oncolytic virus targets cancer cells, without affecting normal cells, by replicating within cancer cells, leading to cancer cell lysis, at the same time, 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
of immune checkpoint inhibitors in low- or non-reactive tumors.

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
at the non-injection site.
Intravenous oncolytic virus can target all tumor sites, thereby improving efficacy
.
However, intravenous injection causes the body to produce antiviral neutralizing antibodies, which severely limits subsequent repeated administration
.

To maximize the potential of viral immunotherapy, strategies must be developed to avoid neutralization of antibodies in the human body
.
Heavy targeting, cell carriers, polymer coatings, and liposomes have been used to protect oncolytic viruses from neutralizing antibody effects, but these studies have not yet progressed to the clinical stage
.
The widespread adoption of mRNA vaccines in recent years has paved the way for the development of lipid nanoparticles (LNP) vector systems and holds promise
for overcoming the challenges of intravenous administration.

On October 7, 2022, researchers at Oncorus, an oncolytic virus therapy development company, published in the journal Nature Communications: Development of intravenously administered synthetic RNA virus immunotherapy for the treatment of cancer Research papers
.

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
of oncolytic viruses.

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 genomes of these two viruses are righteous single-stranded RNAs that, after entering tumor cells, are sufficient to initiate the viral life cycle
.
The study reported RNA viral genome (vRNA) delivery and replication
of synthetic SVV and CVA21.


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
of PD-1 inhibitors.
This synthetic viral platform will address the limitations of repeated intravenous administration of oncolytic viruses and improve the therapeutic potential
of oncolytic viruses.


Oncorus Corporation is a clinical-stage oncolytic virus therapy development company founded in 2015 and listed on the NASDAQ in October 2020, with a initial market capitalization of $340 million, but currently has a market capitalization of only $20 million
.


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 genomes (vRNAs), namely ONCR-021 and 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, and melanoma, and are expected to submit IND applications
to the FDA in mid-2023 。 The latter encodes optimized Seneca Valley virus (SVV), used to treat small cell lung cancer, prostate cancer, and other neuroendocrine cancers, and will file IND applications
after ONCR-021.


References: open reprints welcome to the circle of friends and WeChat groups