Cancer Cell-Killing Oncolytic Virus... The Rise of Vaccinia Virus-Based Therapies

Proliferates and Destroys Cancer Cells
Hundreds of Billions in Overseas Technology Contracts
Domestic ShillaGen SJ-600 Series in Spotlight

[Asia Economy Reporter Lee Gwan-ju] When it comes to viruses, people basically think of 'pathogens.' Well-known examples include the SARS-CoV-2 virus that caused the COVID-19 pandemic, influenza viruses, and noroviruses that cause acute gastroenteritis. However, recently, research using viruses to treat diseases has been actively progressing. A representative example is the 'oncolytic virus,' which is gaining attention as a next-generation anticancer agent.

'Oncolytic Virus' That Proliferates and Destroys Cancer Cells

An oncolytic virus is a genetically engineered virus with infectivity that proliferates within cancer cells and destroys them. When an oncolytic virus is introduced into the body, the virus invades cancer cells, repeatedly proliferates, and eventually causes the cancer cells to die, releasing their contents outside the cells. As the cancer cells burst, hidden antigens are exposed, inducing the body's immune response. This mechanism not only directly kills cancer cells but also activates the immune system to exert anticancer effects. The antibodies generated during this process remember the cancer cells and help suppress cancer recurrence.

Amgen's oncolytic virus-based melanoma treatment 'Imlygic'
[Photo by Amgen]

The world's first oncolytic virus therapy is Amgen's 'Imlygic.' It was officially launched after receiving approval from the U.S. Food and Drug Administration (FDA) in October 2015 and is used as a treatment for melanoma, a type of skin cancer. However, Imlygic is based on the herpes simplex virus (HSV), which presents certain limitations. It is effective only against cancers expressing the Ras gene and must be directly injected into the cancer site to be effective, limiting its use to cases like skin cancer where the tumor is visually identifiable. Another drawback is that genes involved in herpesvirus replication are removed, reducing the replication ability, which is a core principle of oncolytic viruses.

Therefore, recent research has been actively developing oncolytic viruses based on new viruses. Oncolytic viruses using the vaccinia virus, which was used in the smallpox vaccine, are known to have several advantages. First, the large genome size allows the incorporation of multiple anticancer (therapeutic) gene materials. It also has significant safety advantages. Since it was used in the smallpox vaccine, its safety for human administration has been proven over a long period.

Representative companies developing oncolytic virus therapies include Calivir, ViroCure, and Pfizer. Calivir, a U.S.-based oncolytic virus specialist, developed the 'VET' (Vaccinia Enhanced Template) platform based on the vaccinia virus and signed a technology export contract worth up to $634 million (approximately 780 billion KRW) with Astellas in 2020. Calivir also signed a license-out agreement with Roche last year, but the contract amount was not disclosed by mutual agreement.

Active Domestic Companies... SillaJen Announces Preclinical Results of 'SJ-600'

A representative domestic company developing oncolytic viruses is SillaJen. The preclinical results of the vaccinia virus-based 'SJ-600' series developed by SillaJen were recently published in the official journal of the American Association for Cancer Immunotherapy, the Journal for ImmunoTherapy of Cancer (JITC). According to the paper jointly submitted by SillaJen and Professor Lee Dong-seop's research team at Seoul National University College of Medicine, the SJ-600 series expresses the complement regulatory protein 'CD55' on the viral envelope, enabling the oncolytic virus to survive stably in the bloodstream. It can be administered systemically via intravenous injection, allowing direct drug delivery not only to solid tumors but also to metastatic cancers. Another advantage is that multiple anticancer gene materials can be loaded onto a single virus, maximizing anticancer effects.

Sillajen.

SJ-600 removes the thymidine kinase (TK) gene necessary for self-replication from the vaccinia virus. When SJ-600 is administered through blood vessels, the oncolytic virus searches for the TK gene and attaches to cancer cells rich in the TK gene. While SJ-600 absorbs the TK gene, the cancer cells can no longer proliferate and are destroyed. At this time, immune cells attach and kill the cancer cells.

Notably, when SJ-607 was administered, antibodies against the virus were formed, but resistance to neutralizing antibodies that interfere with the virus infecting and killing cancer cells was observed. This means that the efficacy of the oncolytic virus does not decrease, allowing for repeated administration. Periodic administration can reduce the dosage, minimizing anticancer side effects.

A bioindustry official explained, "The vaccinia virus was used as a smallpox virus vaccine for about 200 years, with millions of people vaccinated, accumulating extensive experience." He added, "Since it is a virus with a certain level of guaranteed safety and efficacy, it has strengths in the oncolytic virus therapy market."