Double trouble; Activating cancer prodrugs by leveraging a tumour selective oncolytic virus
Dr Alan Cameron in the laboratory (photo supplied).
Oncolytic viruses (OVs) are an emerging class of cancer treatment that selectively infect and kill cancerous cells without infecting or harming healthy tissue. However, OV therapies suffer from certain limitations, perhaps the greatest of which is virus clearance by the patient immune system before complete tumour destruction. To increase their efficacy, OVs could be used in combination with chemotherapeutics or radiotherapy. The presence of viral infection at the tumour site offers new opportunities to develop innovative prodrugs. This project seeks to develop a novel combination therapy platform. A promising OV, Seneca Valley Virus (SVV) will be combined with a cytotoxic prodrug and release the payload selectively at the tumour site. Cytotoxic payloads will be conjugated to an inactivating peptide sequence that is selectively cleaved by the viral protease of SVV. This cleavage will release the active cytotoxin specifically in the tumour environment to provide an exciting new combination therapy approach to cancer treatment. The cancer will now experience 'double trouble' as it is destroyed by direct cytotoxic effects of both the oncolytic virus and the cytotoxic drug. The classical side effects of the cytotoxic chemotherapy drug will be significantly reduced by its specific activation only at the tumour site by SVV.