Shaping the immunogenicity and efficient range of oncolytic vaccinia virus by the programmed release of therapeutically active, self-amplifying RNA containing virus-like-particles
In this project, an oncolytic virus will be generated that combines the safety profile of vaccinia virus, with the immunostimulatory power of RNA-vaccines. Currently, the RNA-genomes of Alphaviruses are successfully used to encode proteins to be vaccinated against. Their special genome organization and makeup allow them to self-amplify within a cell. This replication in turn alerts the immune system to the host cell while creating an abundance of not only the antigen to be vaccinated against, but also therapeutically active proteins, e.g. immune checkpoint inhibitors, that can be released to neighboring cells. The RNA-genome of Semliki-Forest Virus was encoded into the DNA-genome of vaccinia virus in a way that it will be directly packaged into so called virus-like particles and shuttled to cells in the surrounding. As vaccinia virus has multiple ways to hide itself from the immune system, an infected cancer cell will therefore release numerous particles that are able to transduce non-infected cancer cells and activate the immune system. Eventually, the initial infection will be cleared together with the remaining tumor cells. The benefit for Turnstone Biologics is therefore the generation of a novel, improved oncolytic virus which will be based on Turnstone's proprietary viral platform.