Viruses fight cancer

By on February 22, 2013

Viruses have a bad rap. After all, they spread from person to person, causing disease. Scientists, however, have been long using viruses for good in genetics as vectors for transfecting cells with new DNA. For the past 20 years, researchers have also been attempting to rework viruses to treat cancer instead of causing disease. Though there have been successes in small trials in which tumors shrunk dramatically when infected, cancer-fighting viruses have never had big gains.

Diagram of componets of an RNA virus. www.microbiologie-medicale.fr

Diagram of componets of an RNA virus. www.microbiologie-medicale.fr

Recently, however, a group of researchers from South Korea, Canada, and the United States have made another stride in moving these viruses into the clinic. Unlike the previous attempts, this new virus has a backup plan if it fails to kill cancer cells – it calls for reinforcement from the body’s immune system.

The basic idea behind these cancer-killing viruses is that they are mutated to infect only cancer cells. Viruses need a specific set of conditions in the environment in order to survive and reproduce. Decades of research have revealed several mutations that prevent viruses from surviving in normal cellular conditions.

Cancer cells, however, are mutated versions of normal cells and thus have a different cellular environment. If a virus could be engineered to survive in an only-cancerous environment, it would kill off the tumor without affecting healthy cells. The scientists took the JX-594 vaccinia virus, a relative of smallpox, and disrupted the viral thymidine kinase gene, which is critical for the virus to replicate. Cancer cells, which activate the human analog of this gene, create an environment that allows the virus to replicate.

In addition to the disrupted gene, the scientists inserted the gene for human granulocyte-macrophage colony-stimulating factor (hGM-CSF) into JX-594. When expressed, this gene promotes the immune reaction to cancer cells. Any cancer cells that survived the viral attack would have to face a second assault from the body.

The study, published in Nature Medicine, tested the human response to the virus. Most patients only suffered some mild flu-like symptoms, and only 1 out of the 30 subjects suffered a strong reaction. The patients were divided into two groups – low and high dosages. Both groups had a markedly higher survival rate. Whereas the normal expected survival time would be two to four months, the low-dosage group survived nearly seven months and the high-dosage group survived over a year.

Viral treatments are extremely promising in that they can overcome one of the biggest hurdles in treating cancer – halting metastasized cancer cells. Once cancer cells start to move across the body, they become increasingly difficult to detect and kill. Because of their selectivity for cancer cells, however, these specially engineered viruses can be spread across the body, killing any cancer cell it comes across while leaving healthy cells intact.

Despite the promises, this modified virus has many hurdles to overcome. It is still in a Phase 2 trial, which tests drugs on a small scale. It must pass this trial and then a large-scale Phase 3 trial in order to move into the market. Once there, however, viruses will certainly revolutionize cancer treatment.

Tianjiao Zhang
Staff Writer
tzhang@uab.edu

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