There has been recent publications from scientists looking into how modifying viruses could lead to a new form of cancer treatment. These oncolytic viruses have been used in early phase clinical trials for paediatric solid tumour and small cell lung cancers and shown to initially be effective in binding to these cancerous cells.
The virus is known as the Seneca Valley Virus has shown to attach to a receptor known as tumour endothelial marker 8 (or anthrax toxin receptor 1) which is overexpressed on the surface of tumour cells, in the majority of human cancers. In previous oncolytic virus development, a problem arose from the fact that many viruses not only bound to anthrax toxin receptor 1 but also anthrax toxin receptor 2. The problem with this is that normal, non-cancerous human cells express the anthrax toxin receptor 2. However, the Seneca Valley Virus showed high affinity for the anthrax toxin receptor 1 and not 2. The virus acts as a ligand for this receptor, currently this virus just marks this cell as a cancerous cell it doesn’t destroy it. However, this offers great potential in targeted cancer therapy. Another issue that has come up within clinical trials is that the body’s natural immune system is programmed to fight off viruses such as Seneca Valley Virus. Within the trails it was shown that the immune system destroyed the virus within 3 weeks of treatment, the host developed immunity. Therefore further research is needed into the structure of the Seneca Valley Virus and it’s capsid in order to determine the interactions between the virus and antibodies that the body’s immune system produced to attack this, and to identify and key components within the capsid surface that are involved in these interactions in order to try and prevent the development of immunity to the virus. There has been some research into this and it unfortunately suggests that the anthrax toxin receptor 1 binding site and that that binds the antibodies overlaps. This could mean that modifying the virus capsid in order to prevent the immune system destroying the virus would also render the virus unable to bind to the anthrax toxin receptor 1 and therefore be useless as a cancer treatment. More research is need into mutations of the capsid in order to determine if it could be used as a oncovirotherapy and evade the host immune system.
The full article can be read here: http://www.pnas.org/content/early/2018/10/30/1810664115