Cancer is a disease characterized by the uninhibited proliferation of cells. In the body, normal cells go through a cycle (grow, divide, then die) in a repetitive fashion. In the early stages of growth in a human, cells divide at a fast rate, until the person becomes an adult, at which time the cells divide only to replace worn-out cells or dead ones. Since the abnormal cancer cells divide at an uncontrollable rate, they outlive normal cells in the body, and instead of dying, they continue to divide and form new abnormal cells.

Existing cancer therapies, such as chemotherapy, aim to kill these cancerous cells but in doing so also kill normal cells.  The therapeutic index of chemotherapy is reported as 6:1 which means that for every 6 tumour cells killed by chemotherapy, one normal cell is killed. The negative effects of conventional cancer therapies have inspired the search for novel strategies to kill cancer. One such approach is to harness the natural properties of viruses to aid in the fight against cancer. 

The exciting field of oncolytic virus therapy is now being tested in limited clinical trials around the world.  One of the benefits of oncolytic virus therapy is that the therapeutic index has been found to be as high as 100,000:1 which makes it appear to be a superior cancer treatment.

Herpes Simplex Virus type I (HSV-1) is an excellent candidate for cancer therapy as it has broad tissue specificity, replicates to high titres, kills infected cells, is easy to manipulate and can tolerate large insertions into its genome. From a safety standpoint, anti-herpes drugs are available as a safeguard against unwanted replication and the virus does not insert into host cell nucleic acid, eliminating the fear of insertional mutagenesis. During tumor evolution, diminished interferon (IFN) responsiveness is a common genetic dysfunction3. IFN is a multi-functional cytokine with potent anti-proliferative and antiviral activities. Thus viruses, or virus mutants, whose replication inhibited by IFN should preferentially replicate in cancerous cells and not normal cells.

KM110red (KM110r) is a double mutant HSV-1 bearing lesions in the ICP0 gene, which has been shown to function in part to overcome IFN-mediated anti-viral activities, and VP16, a virion  associated viral transactivator. Therefore KM110r should fail to replicate in normal fibroblasts, and efficiently propagate on cancerous cells, making it a potential oncolytic virus for cancer therapy.

This novel experimentation aims to evaluate the efficacy of double-mutant Herpes Simplex Virus type I called KM110r, and in doing so explain why the virus may be safe in normal tissues.