*4.9. Oncolytic Vaccinia Virus*

Vaccinia virus is a double-stranded DNA virus that belongs to poxvirus family [154]. Its natural tropism to enter the CNS has made it an attractive candidate for systemic delivery in GBM patients [155]. A phase I/II clinical study for GBM patients is currently ongoing (NCT03294486), in which patients are treated systemically with the vaccinia virus TG6002 [156]. Different strains of oncolytic vaccinia virus have been applied for other types of cancer as well and researchers tried to identify predictive response markers [157]. Zloza et al. identified the inhibitory molecule immunoglobulin-like transcript 2 (ILT2) on the cell surface of T cells, as a potential biomarker for vaccinia virus immunotherapy in melanoma patients. Increased expression of ILT2 on T cells was associated with poor response to oncolytic virotherapy using vaccinia virus [157]. Another study attempted to identify biomarkers associated with resistance to vaccinia virus therapy in hematological malignancies [158]. Genes involved in the ubiquitination pathway, DNA damage response and antigen presentation, among others, were identified and associated with resistance to vaccinia virus-induced oncolysis [158].
