Grant: Travel Awards - Institute Community Support

The existence of naturally occurring viruses which preferentially target and replicate in tumour cells has given birth to the field of Oncolytic Virotherapy. The incredible success of this field in the last decade is being marked by numerous clinical trials and the recent FDA approval of the first oncolytic virus. Recent studies have shown a Vaccinia poxvirus to be an excellent candidate as a clinical therapeutic. Pexa-Vec (formerly JX-594) been engineered with a high safety profile and has been shown to persist within tumour cells in humans while expressing oncolytic transgenes. Although the success of Pexa-Vec is remarkable, little is known about the oncolytic potential of other Vaccinia virus strains. The present work sets to address this issue by first comparing five common strains of Vaccinia virus in co-infection experiments both in vitro and in vivo using next generation sequencing. Our preliminary results suggest a significant competitive advantage that is possessed by the Copenhagen strain, which is able to quickly outgrow its competitors in various cancer cell lines and human melanoma specimens. We aim to continue screening resistant cancer cells lines with our competition assay in an effort to establish which strain possess the best oncolytic engine. The fittest strain will then be further characterized in terms of safety using in vivo bio-distributions, ability to incite an anti-tumour response and ability to kill tumour cells. Overall this research provides fundamental information about the genetic fitness and oncolytic capacity of common Vaccinia virus strains. This information is certain to have direct implications on the future design of the next Vaccinia virus-based oncolytic.