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Oncolytic virus therapy


Cancer is the leading cause of death among Japanese people. It is responsible for more than 300,000 deaths annually. The most common cancer treatments include surgery, radiation therapy, use of cancer-targeting drugs, and immunotherapy. However, many concerns related to the efficacy and side-effects of these treatments still remain. For example, a tumor that is not completely removed by surgical procedures may metastasize, or cancer patients may suffer from side-effects (vomiting and hair loss) caused by anticancer agents.

Since the 1990s, various countries worldwide have been researching a new form of treatment, called oncolytic virus therapy, with the hope of overcoming the problems associated with existing procedures. This treatment relies on recombination of viral genes such that cancerous cells are specifically targeted during infection. Per its natural infective cycle, the virus infects cancerous cells, causing them to rupture and release viral progeny—in this way proliferating until all cancerous cells are eliminated. In addition, a new generation of virus has recently been developed that is detected by the host immune system, inducing an immune response that ultimately destroys even those cancerous cells not infected with the virus.

Anticipated advantages of oncolytic virus therapy include the following:  

•    May be applied to all solid cancers, including those in regions difficult to treat, such as the brain
•    May be used in combination with existing chemo- and radiation therapies
•    May be repeatedly administered (unlike anticancer agents) as it does not affect the bone marrow, and is free from other side effects
•    Enhanced anti-tumor efficacy may be achieved by incorporation of other therapeutic genes (e.g., cytokine genes) directly into the viral genome.

Furthermore, the availability of antiviral drugs allows for interruption of therapeutic effects at any time during the course of a patient’s treatment.

G47Δ and Dr. Tomoki Todo

Dr. Tomoki Todo, a professor at the University of Tokyo’s Institute of Medical Science, is at the forefront of Japan’s oncolytic virus therapy research. Original studies conducted in the United States described the successful development, as well as early clinical studies, of G207, a recombinant virus based on the herpes virus, HSV-1. G207 was designed to possess qualities uniquely advantageous for combatting cancerous cells. Dr. Todo has now developed G47Δ, a third-generation HSV-1 virus, with improved anticancer capabilities. G47Δ induces a strong immune response targeting patients’ cancer cells, and exhibits enhanced anticancer activity compared to G207. Moreover, while European studies using similar viruses failed to demonstrate complete elimination of pathogenicity against non-cancerous cells, G47Δ has been shown to be uniquely target-specific in animal experiments.

Current and future prospects for cancer treatment

Clinical research of G47Δ in Japan was launched in 2009, first as treatment for brain tumors, and then, in May of 2013, for prostate cancer. Clinical studies for the treatment of olfactory neuroblastoma have also been underway since September 2013. These studies of oncolytic virus therapy using G47Δ in human patients represent the world’s first.

Japan boasts of world-class, cancer-related, medical technology and treatments. However, due to the rapidly aging population and a shortage of human resources in the medical sphere, both prevention and treatment of cancer have been insufficient. As a result, the number of cancer patients in Japan continues to increase. Oncolytic virus therapy has a wide range of applications and is highly anticipated to be implemented for a variety of practical uses.  Thus, while the dissemination and application of oncolytic virus therapy in Japan is expected to directly promote the development of cancer treatments, it may also have a broad impact on viral therapies for use in other medical fields.

11 December, 2014
About the author
Hiromi Jitsukata is a reporter for Japanest NIPPON
(The Institute of Medical Science, The University Of Tokyo)