*3.7. Rrp450*

Rrp450 is a genetically engineered oHSV with a deletion of ribonucleotide reductase gene *ICP6* as well as an insertion of the *CYP2B1* gene, thereby diminishing replication potency in non-dividing cells and encoding for a cytochrome of the P450 family that activates the prodrug cyclophosphamide [60]. Pawlik et al. demonstrated in in vitro and in vivo models of hepatocellular carcinoma that Rrp450 causes tumor cell death, which is augmented by additional administration of cyclophosphamide [61]. These results were confirmed in preclinical models for sarcoma, high-grade medulloblastoma, and atypical teratoid/rhabdoid tumors [62,63]. The first phase I study for assessment of safety and tolerability of Rrp450 in liver metastases or primary liver cancer is currently in the recruitment phase (NCT01071941).
