Improving the Safety of Viruses That Treat Cancer

Investigators working with colleagues in Germany have created a greatly needed multilevel safety approach for viruses used to treat cancer. In the process of devising cancer-killing viruses more specific to cancer tumor cells, they reported having enhanced the therapeutic effectiveness of viruses. They achieved this by engineering a modified measles virus that is activated only in the presence of secretions specific to malignant cancer cells.

In effect, the Mayo Clinic virus modification, performed by researchers at the Mayo Clinic (Rochester, MN, USA), utilizes proteins secreted by cancer cells as the distinctive basis to the virus' ability to be activated. Their study was published in the August 1, 2006, issue of the journal Cancer Research.

The study was performed in laboratory mice that were transplanted with a form of human cancer. The process is still in its research phase, and therefore, years away from clinical use in humans. However, the Mayo findings may be immediately useful in creating improved cancer therapy for humans. "Our work shows that oncolytic measles virus particle activation can be made dependent on substances secreted by cancer cells, and this enhances safety,” explained Roberto Cattaneo, Ph.D., lead researcher on the Mayo team. "By doing this, our study broadens the safeguarding strategies possible to tightly restrict the targeted virus to cancer cells.”

The researchers say their study is a major development because it provides a way of designing a therapeutic virus that is safe, stable, and that accurately targets and destroys cancer cells. Significantly, it appears to greatly reduce the possibility that the virus would erroneously turn on and harm the patient by causing unintended infection.

This advancement of the cancer-activated virus is a helpful safety development for the promising experimental field of "oncolytic virotherapy.” The term refers to the natural ability of specific viruses to kill cancer cells. It is a promising approach that has been known for a long time, but limited by safety concerns. The measles virus is one example of an oncolytic virus. For example, the live attenuated Edmonston measles vaccine strain can decrease or eliminate human lymphoma, myeloma, ovarian cancer, and glioma tumors that are transplanted into laboratory mice.

The success of oncolytic virotherapy depends on limiting the viral growth to cancer cells--and only cancer cells--to prevent unintentional rogue infections elsewhere in the healthy body. The Mayo cancer-activated virus generates one more component of a multiple safeguard system, so it now consists of three levels. The resulting enhanced security system now works at the level of activation of the virus particle; receptor recognition necessary for the virus to enter a cancer cell; and the ability of the virus to multiply preferentially in cancer cells. These multiple safeguards are specific to and dependent on cancer cells, and are therefore crucial to fully converting viruses into safe therapeutic agents.



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