Fig. 1

Mechanism of Oncolytic Virotherapy. When oncolytic viruses enter normal cells, the antiviral responses inhibit viral propagation. In cancer cells, aberrant signaling mechanisms lead to blockage of antiviral responses. Oncolytic viruses thus replicate and lyse host cancer cells that lead to release of virus in the immediate milieu. The released virus can infect nearby cancer cells which present with tumor-associated antigens and viral antigens that mediate anti-tumor responses. Only the replication-competent oncolytic viruses have the capability to replicate in cancer cells. Inset, the working model of the replication competent adenoviral gene therapy vector developed at Henry Ford Health that harbor two suicide genes. Gene products from these suicide genes (cytosine deaminase; CD, and thymidine kinase; TK) interfere with de-novo and salvage DNA replication pathways, that lead to enhanced cancer cell-killing when combined with cytotoxic chemotherapy or radiotherapy