Cancer is a chronic disease in which leads millions of people to die every year from worldwide. According to the World Health Organization (WHO), there are about 18 million people diagnosed with cancer worldwide in 2018, and more than 9 million people will die of cancer. By 2030, the number of newly confirmed cases will exceed 23 million each year. The most common types of cancer include lung cancer, breast cancer and colorectal cancer.
Researchers around the world have tried to discover new cancer treatments in recent years, and viral therapy has attracted the attention of many scientists. Virological therapy is a treatment that uses biotechnology to convert certain viruses into anti-disease drugs, including oncolytic viruses that infect and destroy cancer cells.
Oncolytic viruses have unique properties which make them different from other cancer therapies. The advantages of viral therapy include lack of cross-resistance with other therapies and the ability to destroy tumors using a variety of mechanisms. In order to find a new way to selectively kill cancer cells, scientists have been focusing on oncolytic viruses. A new study tested the behavior of an anti-cancer virus that is perfectly suited to tumor cells but keeps healthy cells intact.
Seneca Valley Virus (SVV) is an oncolytic virus which is expected to be the next breakthrough cancer treatment. Researchers at the Okinawa Institute of Science and Technology (OIST) in Japan and the University of Otago in New Zealand described the behavior of the virus in a study published in the journal of PANS. This study explains how SVV interacts with tumors without affecting healthy cells.
In order to test the behavior of the virus, scientists used cryoelectron microscopy to capture images of thousands of particles and observe their structures at high resolution. Understanding the structure of these particles is the key to creating an effective anti-cancer virus that can be applied to develop new drugs and therapies.
Figure 1. Cryo-EM structure of the SVV-ANTXR1 complex.
SVV is unusual because it targets specific receptors in tumor cells, that is, the anthrax toxin receptor 1 (ANTXR1) which is only present in tumors, however, the close relative of the receptor, ANTXR2, is only found in healthy tissues. SVV can bind to ANTXR1 in tumors, but not binding to ANTXR2 in healthy cells. The behavior of this virus makes it suitable for the treatment of a variety of cancers, as the ANTXR1 receptor is present in tumor cells of more than 60% of human cancers.
‘The difference between the two receptors is subtle, but nonetheless, these subtle differences make one of them Viruses combine, while others don't. These combinations must be as closely matched as keys and locks. This is a highly evolved system where everything fits perfectly.’ claimed by Professor Matthias Wolf, head of the frozen electron microscopy department at OIST, one of the study's co-authors.
Researchers have used SVV for early clinical trials of pediatric solid tumors and small cell lung cancer. The virus exhibits anti-cancer properties for both diseases. However, the immune system is programmed to fight these viruses and eliminate perceived threats within three weeks. The researchers believe that analyzing the structure of SVV can help find ways to evade the immune system, allowing the virus to replicate and kill cancer cells.
Professor Mihnea Bostina, co-author of the study and the academic director of the Electron Microscopy Center at the University of Otago, said, ‘If we can figure out which parts of the virus are necessary for binding to the receptor and which are not, as a result, we can try to change these non-essential parts so that the virus can escape the attack of the immune system without affecting the necessary parts to bind to the receptor.’
Although scientists are still looking for an effective way to evade the immune system, Professor Wolf's team believes that it can be modified to identify different receptors by modifying the SVV, which will make the virus an excellent weapon for fighting different types of cancer.
Nadishka Jayawardena, a graduate student at the University of Otago, and the first author of the study, he believes the study will produce effective and powerful cancer treatments in the near future.
Reference
Nadishka Jayawardena, Laura N. Burga, Richard A. Easingwood, et al. Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus. PNAS. October 3, 2018