Encoding Bi-specific T cell Engagers into oncolytic vaccinia virus
Through engineering and selection strategies, we have created novel cancer-killing oncolytic viruses (OVs) that are selective for tumours but are unable to grow in normal tissues. A critical component of the therapeutic activity of this class of therapeutics is the induction of an anti-tumour immune response, which can be suppressed in many tumours. One strategy to circumvent this problem is the use of Bi-specific T cell Engager (BiTE) antibodies that are able to force T cell recognition and killing of tumour cells. For many BiTEs in clinical development, there are toxicities associated with systemic administration and challenges to reaching high enough local concentrations in solid cancers. For Turnstone Biologics, we will engineer OVs to produce BiTEs in tumours, where these antibodies are only needed in picomolar concentrations to be effective. We predict that expression of BiTEs from our potent oncolytic viruses can lead to improved outcomes with reduced off-target toxicities.