Novel Research Discovers More Value of Oncolytic Viruses

Viral therapies for cancer treatment have been investigated since the 19th century, but due to technical barriers and safety issues in genetic engineering, there has been no great progress until the last two decades. Currently, the main methods of viral use as oncology therapies are viral vectors for gene therapy and oncolytic viruses (OVs).

Currently, there are five OVs approved for marketing worldwide, which are predicted to reach a market of over $10 billion in the future. Popular research targets include IL-12, GM-CSF, PD1, IL-15, PDL1, CD, CD19, CTLA4, NIS, etc.

At present, there are many lysosomal viral drugs in clinical development, and this article will introduce some of the drugs that are in the leading stage of clinical development.

1. CG0070

CG0070 is a genetically modified adenovirus type 5 (Ad5) that is modified to contain the cancer-selective promoter E2F-1 and the immune cell-stimulating factor GM-CSF gene, which selectively replicates and lyses tumor cells within Rb-regulated defective tumor cells. Rupture of cancer cells releases tumor-derived antigens and GM-CSF expressed along with the virus, thereby stimulating a systemic anti-tumor immune response.

2. Pelareorep

Pelareorep (AN1004) is a non-pathogenic, unmodified oncolytic reovirus that overcomes the effects of neutralizing antibodies and selectively infects and destroys tumor cells by activating the body's autoimmune system for the treatment of a variety of solid tumors and hematologic malignancies. Pelareorep is the most advanced oncolytic virus product available for intravenous administration in the world. Its Phase II trial in metastatic breast cancer found that pelareorep in combination with paclitaxel doubled overall survival in patients with ER+PR+/HER2- breast cancer (21.8 months vs. 10.8 months). In its global Phase II clinical trial (BERIL-1) for the treatment of head and neck squamous cell carcinoma (HNSCC), patients had a median survival of 10.4 months. In March 2022, Oncolytics Biotech announced the completion of the pelareorep Phase 1/2 GOBLET study in the metastatic colorectal cancer (mCRC) cohort safety evaluation in three patients.

3. Pexastimogene devacirepvec

Pexastimogene devacirepvec (JX-594) is a genetically engineered cowpox virus with mutations in the TK gene and insertion of the human GM-CSF gene to enhance the antitumor immune response. Previously, the drug had poor phase III clinical performance in hepatocellular carcinoma and is currently being evaluated for efficacy in combination with cemiplimab for renal cell carcinoma.

4. Olvimulogene nanivacirepvec

Olvimulogene nanivacirepvec (GL-ONC1, Olvi-Vec) is an oncolytic vaccinia virus developed by Genelux by replacing the viral TK, hemagglutinin and F145L genes with three expression cassettes encoding?-galactosidase,?-glucuronidase, and renin luciferase/green fluorescence (RLuc-GFP) fusion proteins, respectively. A phase I clinical trial of GL-ONC1 in patients with head and neck cancer showed that intravenous GL-ONC1 combined with standard chemotherapy improved overall survival.

5?OH2

OH2 (BS001) is the world's first oncolytic virus candidate that selected oncolytic herpes simplex virus type II (HSV2) as the vector and entered clinical trials. Clinical data showed that BS001 achieved an objective remission rate (ORR) of 30%, a disease control rate (DCR) of 50%, and a one-year survival (OS) rate of 93%. In addition, the latest clinical data for the treatment of colorectal cancer showed that the objective remission rate of BS001 injection in clinical monotherapy for colorectal cancer patients has exceeded 10%; the objective remission rate of BS001 injection in combination with PD-1 monoclonal antibody reached 18.2%.

In recent years, with the development of genetic engineering technology, the understanding of the function and structure of viral genes has been deepened, and the optimal design and manipulation of the viral genome to produce non-pathogenic viruses has become the direction of OV research, which has greatly promoted the progress of oncolytic virotherapy. It is believed that this strategy will play a wider and deeper role in the treatment of human diseases.

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