Dual function engineered oncolytic viruses may emerge as new hope in treating cancerous tumors

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Photo Credit: J cell bio. April 2005. CC by 4.0 . Cell infected by Vaccinia virus


Oncolytic viruses are designed to kill cancer cells and treat one form of skin cancer. These viruses are being extensively tested as treatments for other cancers. 

In a new study, it has been found that these viruses can be further improved to strengthen the body's response against tumors. Researches have discovered that this new type of oncolytic virus, while being able to kill cancer cells can also cause immune cells to be drawn into tumors along with a hormone that they need for their own cell-killing function.

In September 17 in Immunity, the findings of the study were published where mice with melanoma tumors were studied. The dual-function virus was more effective at shrinking and removing tumors than the standard oncolytic virus.

Philip Daschner, program director in NCI's Division of Cancer Biology, a stranger to the study explained, "The new thing here is that this virus has been engineered to relieve immunosuppression. It's an idea that may be quickly translated to use in patients." 

How these viruses work

The viruses enter tumors cells and replicate therein, which breaks them apart. In this rupture, tumor cell proteins get released into the bloodstream and these can be recognized by the immune system as tumor antigens. This process can draw T cells into a tumor to start killing cancer cells, and potentially may even trigger them to recognize metastatic cancer elsewhere in the body.

According to Dr. Greg Delgoffe's, Ph.D., of the University of Pittsburgh Medical Center, who led the study on mice explained, "The tumor environment by it's own is very toxic. When T - cells get in, they experience a harsh, low-oxygen, desert-like landscape." This environment may affect the ability of immune cells to function.

Dr. Delgoffe's lab also explained exhaustion - the fading away of killing ability of T-cells.

To enhance the ability of the virus, the research team wanted it to secrete something into the toxic environment to support the T cells.

*Leptin Hormone as supporter for T cells.*

Leptin, known for regulating hunger and body weight, is also needed by the immune cells. Researches found that tumors had low levels of leptin and also T cells, especially the exhausted ones had high receptors for it.

Leptin was identified to enhance the tumor cell killing ability of T cells. This eventually, the oncolytic virus was redesigned to carry the gene for leptin production by Dr. Delgoffe's team. 

On the injection of reengineered dual function virus into the mice, the tumors were significantly shrunk and removed in about a quarter of the mice.

Preventing Cancer recurrence

Further studies by Dr. Delgoffe's team suggested that the engineered virus had informed and prepared the immune system to remember and recognize the tumor cells ( immune memory ). 

“It’s very exciting that there’s some evidence of immune memory against tumors,” Daschner said. “If this could work the way a vaccine works, hopefully patients would develop immunity that could prevent tumor recurrence.”

Before testing the virus in people, Daschner believes, further studies are required. Since direct injection of the virus into tumors would not always be feasible, an understanding of its injection into the bloodstream is to be made.

Another exemplary initiative of studying microorganisms for potential cancer treatments is NCI's Bugs as Drugs. It is supporting research on bacteria and bacteriophages for treatments. Bacteriophages are tiny viruses that infect bacteria.

Daschner remarks on such endeavors by saying, "It is a very exciting class of potential new therapies."



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