A recent publication from Bill Kaiserâ€™s and Ed Mocarskiâ€™s labs in Cell Host & Microbe touches on a concept that needs explaining: oncolytic viruses.
Viruses have been subverting the machinery of healthy cells for millions of years, and many viruses tend to infect particular tissues or cell types. So they areÂ a natural starting point for researchers to engineer oncolytic viruses, which preferentially infect and kill cancer cells.
Several oncolytic viruses have progressed to advanced clinical trials. Amgenâ€™s â€œT-Vecâ€, a modified herpes simplex virus, could be the first to be approved by the FDA this year based on its efficacy against metastatic melanoma.Â
Winship Cancer Instituteâ€™s Fadlo Khuri was involved in the testing of an oncolytic adenovirus against head and neck cancer earlier in his career. His colleague Erwin Van Meir and colleagues developed (and patented) another adenovirus that selectively targets cells that are not getting enough oxygen, a predicament common to fast-growing cancer cells.
In Cell Host & Microbe, Kaiser, Mocarski and colleagues show how one particular part of herpes simplex virus is critical for overcoming host cell defenses. The HSV enzyme ribonucleotide reductase either triggers or blocks necroptosis, a form of cell death, depending on whether the virus is infecting mouse or human cells.
Ribonucleotide reductase is an enzyme present in our cells too â€“ it converts building blocks for RNA into those needed for DNA. Removing this gene from HSV is part of what makes a modified HSV preferentially replicate in cancer cells, an insightful commentary in Cell Host & Microbe notes. HSV apparently picked up ribonucleotide reductase from a host cell. The enzyme stuck around because it provided an advantage and soon acquired other functions, such as suppressing necroptosis.
Necroptosis is thought to be more â€œnoisyâ€, with respect to the immune system, than its relative apoptosis. Since part of the goal behind oncolytic viruses is to get the immune system to join in the cancer-destroying party, nudging cancer cells to die noisily rather than quietly might form the basis of better therapies.
Note: oncolytic viruses are sometimes described as vaccines. Amgen’s includes a gene for GM-CSF to boost immune stimulation, and the company has been teaming up with makers of cancer immunotherapy antibodies to try its agent in combo with theirs.