*4.3. Arming with Additional Therapeutic Genes*

While these means of targeting aim at enhancing specificity of virotherapy, a number of genetic engineering approaches have been developed to increase antitumor efficacy, often referred to as "arming". First arming strategies aimed at inducing bystander effects in combination radiotherapy and chemotherapy approaches. As mentioned above, MV-NIS allows for concentration of radioactive iodine in infected tumor cells [66].

MeV vectors encoding prodrug convertases were designed for local conversion of prodrugs into active chemotherapeutics. MeV encoding the purine nucleoside phosphorylase, which converts fludarabine into 2-fluoroadenine and 6-methylpurine-2'-deoxyriboside (MeP-dR) to 6-methylpurine, respectively, combined with prodrug administration improved outcome in lymphoma xenograft and immunocompetent murine colorectal cancer models [92,93]. Analogously, MeV was engineered to encode super cytosine deaminase (SCD), a fusion protein of yeast cytosine deaminase and yeast uracil phosphoribosyltransferase, which converts the prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) [94–97].

Other engineering approaches to increase anti-tumor efficacy include insertion of a transgene encoding the proapoptotic protein BNiP3 [49] and the angiogenesis inhibitors endostatin and angiostatin to remodel the tumor microenvironment [98].
