Oncolytic Viruses in the Treatment of Bladder Cancer
Tumor selectivity of oncolytic vaccinia viruses. In normal cells, the wild-type virus encodes a range of gene products that allow virus replication in the cytoplasm of host cells. These products include, but are not limited to, thymidine kinase (TK) and ribonucleotide reductase (not shown), which generate a nucleotide pool to facilitate virus replication. In normal cells, viruses deleted of these essential genes are unable to undergo productive replication. However, in tumor cells, mutations cause dysregulation of numerous pathways, including pathways that allow for unchecked proliferation. One result of these unregulated proliferative pathways is a high level of production of nucleotides, creating a favorable environment for vaccinia virus replication. The mutated viruses are able to replicate, express transgenes (if present), and lyse tumor cells.