oncolytic vaccinia virus T601

A modified, replicative oncolytic vaccinia virus (VV), deleted of the genes for tyrosine kinase (TK) and ribonucleotide reductase (RR), and expressing the yeast-originated, bifunctional cytosine deaminase/uracil phosphoribosyltransferase gene (FCU1), with potential immunomodulating and antineoplastic activities. Upon intravenous administration of the oncolytic vaccinia virus T601, the virus preferentially targets and infects tumor cells, causing oncolysis. In turn, the lysed tumor cells release various tumor-associated antigens (TAAs), which induce an immune response against the tumor cells. Upon concomitant administration of the non-cytotoxic prodrug flucytosine (5-fluorocytosine; 5-FC), the FCU1 expressed in the infected cancer cells produce the enzymes cytosine deaminase and uracil phosphoribosyltransferase which catalyze the conversion of 5-FC into the cytotoxic forms 5-fluorouracil (5-FU) and 5-fluoro-uridilyl monophosphate (5-FUMP); 5-FU and 5-FUMP exert a cytotoxic effect in the infected tumor cells. Double gene deletion (TK-RR-) restricts the propagation of T601 to the tumor cells, thereby reducing toxicity to normal cells.