Frontier|“Take poison to fight poison” to fight cancer, RNA technology is expected to solve the problem of repeated administration of oncolytic virus therapy

▎WuXi AppTec Content Team Editor

Oncolytic viruses (OVs) are promising cancer treatments that selectively kill tumor cells and promote increased levels of inflammation in the tumor microenvironment. Combining OVs with cancer immunotherapy is expected to promote tumor microenvironment remodeling and immune cell activation, and enhance the efficacy of immune checkpoint inhibitor therapy in drug-resistant tumors. Intravenous administration of OVs allows all tumor sites (including small metastases) to be exposed to OVs, thereby improving efficacy. However, neutralizing antibodies against OVs are rapidly produced in humans after intravenous administration, which may impair the therapeutic effect after repeated administration. To maximize the potential of oncolytic virus immunotherapy, researchers have been working to find ways to reduce the adverse effects of neutralizing antibodies.

Oncorus recently published preclinical data on its viral RNA (vRNA)/lipid nanoparticle (LNP) technology in the academic journal Nature Communications, proving the technology It has good performance in virus delivery, selective replication and assembly of virus, tumor cell lysis, etc. It can produce strong anti-tumor efficacy even in the presence of virus-neutralizing antibodies in the blood strong>.

Researchers assembled the single-stranded RNA genomes of two viruses, Coxsackie virus A21 (CVA21) and Seneca Valley virus (SVV), into liposomal nanoparticles for Intravenous use. In previous studies, these two viruses showed strong oncolytic activity and clinical safety, and their genomes consisted of positive-sense single-stranded RNA, which can smoothly start the life cycle of the virus after being injected into tumor cells, making the Oncolytic viruses can replicate in tumor cells. In this study, the authors suppressed tumor growth and avoided the adverse effects of neutralizing antibodies by encapsulating viral RNA in lipid nanoparticles. The results showed that the vRNA/LNP complex was well tolerated, and the replication and proliferation of oncolytic virus particles in tumor-specific regions resulted in the exposure of OVs in tumors far exceeding the requirements for their antitumor activity. Not only that, the replication of OVs in tumors can also promote the infiltration of immune cells into tumor tissues, leading to remodeling of the tumor microenvironment and enhanced activity of anti-PD-1 immune checkpoint inhibitors.

The authors validated the antitumor efficacy of vRNA/LNP in a variety of cancer models (including xenograft tumor models, human xenograft tumor models, genetically engineered murine tumor models, and syngeneic tumor models) Transplantation tumor model), in the small cell lung cancer model, vRNA/LNP therapy brought significant survival benefit to the experimental group of animals.

Image source: 123RF

In conclusion,vRNA/LNP offers a technological approach to cancer therapy that enables repeatable intravenous injection of oncolytic viruses. The tolerability and antitumor efficacy of single or multiple intravenous injections of vRNA/LNP in mouse and non-human primate models support the clinical potential of this therapy. It is reported that Oncorus has developed two vRNA/LNP immunotherapies, ONCR-021 and ONCR-788, and the company plans to submit an investigational new drug (IND) application for ONCR-021 to the US FDA in mid-2023, using the technology into clinical application.

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