Oncolytic Virus-Based Cancer Drugs

Oncolytic (cancer-killing) viruses have tropism for tumor cells, selectively infect or replicate in tumor cells, but spare normal cells. Some of these viruses are naturally attenuated viral strains (such as some strains of reovirus or vesiculostomatitis virus) that more effectively infect or replicate in tumor cells. Others are genetically modified (such as herpes simplex virus type 1 or adenovirus) to mediate oncolytic effects.

Compared with traditional therapies, oncolytic viruses have a high therapeutic index with respect to their ability to kill tumor cells. In some instances, the therapeutic index of oncolytic viruses has been found to be as high as 10,000 to 1, i.e., for every 10,000 tumor cells that are killed, only one normal cell is killed. This is significantly higher than the therapeutic index commonly seen with chemotherapy, 6 to 1, and may result in greater efficacy with fewer side effects.

H101, the oncolytic virus used for head and neck cancer, was approved for use in China. H101 is genetic engineered adenovirus, which selectively replicates in cancer cells and spares normal cells. H101 is a modified version of Onyx-015, lacking E1B-55K and E3 gene functions, and can infect cancer cell, replicate within the cell, and kill the cell through lyses. New viruses released from the lysed cell can infect more caner cells, whereas, H101 does not replicate in normal cell, therefore does not damage the normal cell and causes minimal side-effect.

CG0070, an oncolytic virus with specificity for multiple cancers, is armed with granulocyte macrophage clony stimulation factor (GM-CSF), an immune stimulating hormone. CG0070 can potentially destroy cancer cells through direct cell killing by the virus and through immune-mediated cell killing stimulated by GM-CSF.

Reolysin is a reovirus, named for the Respiratory Enteric Orphan virus. Reovirus is found naturally in sewage and the water supply. The majority of humans have shown evidence of reovirus exposure, but the disease is non-pathogenic, or there are typically no symptoms from infection. The link to its cancer-killing ability was established after it was discovered that the virus grew remarkably well in various cancer cell lines. Reolysin has been demonstrated to replicate specifically in tumor cells bearing an activated Ras pathway. In a tumor cell with an activated Ras pathway, reovirus is able to freely replicate and eventually kill the host tumor cell. As cell death occurs, progeny viruses are then free to infect surrounding cancer cells. This cycle of infection, replication and cell death is repeated until there are no longer any tumor cells carrying an activated Ras pathway.