May 8, 2002 ROCHESTER, Minn. -- If the treatment of cancer is a war -- as declared decades ago -- one of the most daunting problems has always been how to develop reliable reconnaissance once behind enemy lines -- that is, inside the tumor.
Not any more. Mayo Clinic molecular medicine researchers have developed a “cancer snitch.” The snitch is a new elite-force technology: a genetically engineered, trackable virus that can keep doctors informed about the progress of their offensives once they’ve penetrated a tumor. The snitch may become a new weapon in the strategic assault on cancer.
Kah-Whye Peng, Ph.D., and Stephen J. Russell, M.D., Ph.D., both Mayo Clinic molecular medicine researchers, have reported encouraging results about their experiment on mice to find an inexpensive and painless way to get inside information from a cancer tumor under attack by virotherapy. Their results are published in the current issue of Nature Medicine.
Drs. Peng and Russell built their recent study on their previous work in virotherapy, which discovered that a modified measles vaccine virus can be a strong and specific killer of cancer cells.
“Basically, the driver for this research is our keen interest in developing a new approach to cancer treatment using viruses that replicate inside the cancer,” Dr. Russell says. “It’s a captivating concept, but there’s a huge problem. Viruses are sort of wild. After you give a virus, it’s going to spread -- that’s what viruses do -- and there is anxiety with virus therapy about how it will work in different people -- is it getting to the cancer cells; how is it spreading; how fast is it eliminated? And until now, we’ve had no way of answering these questions.”
What were missing, Dr. Russell says, were the basic pharmocokinetics and pharmocodynamics studies. Pharmocokinetics and pharmocodynamics refer to analytical processes in the development of all prescription medicines that reveal many aspects of how a drug affects the body -- not just its therapeutic effects.
According to Dr. Peng, “The most important thing about our work is that now we will help clinicians judge and gauge treatment because we are getting feedback from the patient’s body itself about what the (therapeutic) virus is doing.”
In this latest study, Drs. Peng and Russell took their earlier work with the measles virus a step further by engineering the virus to leak information back to the outside through means of the “snitch.” They did this by engineering into the measles virus the snitch, which is the ability to secrete either one of two markers. One marker is a hormone produced in human pregnancy; the other is a protein found in developing embryos, and later in life, in some cancers. Both these substances are already used as reliable biological indicators.
The result is that the Mayo Clinic’s new trackable virus works to report confidential information from within the body back outside the body to give scientists information that allows them to track biological activity. In the case of the cancer snitch, the activity in question is knowing how effective the modified measles virus is as an anticancer treatment.
“Our research showed the approach works nicely as a way of following the spread of a virus in a living animal,” Dr. Russell says. “We are very encouraged to now be able to intelligently look at what happens inside the body after we have delivered our oncolytic measles viruses.”
Though research is still early, the laboratory results are promising and will likely lead to carefully controlled tests on patients.
“The dream is that trackable oncolytic viruses will be routinely used for cancer treatments in the future,” Dr. Russell says.
Some context for the May Nature Medicine article by Mayo Clinic Molecular Medicine research led by Kah-Whye Peng, Ph.D., and Stephen Russell, M.D., Ph.D.: “Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides,” Vol. 8, No. 5.
The Problem: How to track what is going on within a cancer tumor after a cancer-killing form of measles vaccine virus is administered intravenously to mice -- without inducing the trauma of operating on the animal to examine the tumor. What is needed is information from within the cancer cell through an inexpensive, noninvasive means.
Key Background Information:
1) Viruses are the latest unlikely addition to the cancer armamentarium. Better known for their ability to cause disease and suffering, several viruses have recently been shown to destroy tumors in laboratory mice without damaging essential normal tissues, and a few of these so-called ‘oncolytic viruses’ are currently being tested in clinical trials. The Mayo Clinic molecular medicine research team successfully demonstrated in laboratory mice three years ago that a genetically engineered form of the virus used in the measles vaccine is a potent and selective killer of cancer cells. The term for this approach to cancer treatment is oncolytic virotherapy.
2) The drawback to oncolytic virotherapy has been scientists’ inability to track the effect of the virus once it’s inside the tumor. The lack of a tracking mechanism has thwarted efforts to determine therapeutic effectiveness. But this most recent work by Mayo Clinic’s molecular medicine researchers and reported in the May issue of Nature Medicine may have overcome this problem by engineering a noninvasive marker. The marker is a trackable virus that provides important feedback from within a cancerous tumor through a simple blood test. Think of it as a cancer snitch -- bringing inside information to the outside world for therapeutic ends.
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