Mayo Clinic researchers and their teams are targeting pleural mesothelioma with two very different approaches. One tactic uses a converted virus to carry radioactive iodine to targeted cells. The other examines a new use for an existing drug.
The reason for the studies? Mesothelioma cases have been on the rise in recent years, especially in Minnesota’s northern Iron Range region, where the mining of taconite poses a significant occupational hazard. It is for this purpose that the Mayo Clinic and the University of Minnesota are teaming up to find innovative treatments for this insidious illness.
Re-engineering the Measles Virus
The first method takes the latest version of the measles virus (MV-NIS) and uses it to deliver a treatment that targets and kills mesothelioma cells. The engineered virus delivers this treatment in the form of radioactive iodine, which it injects directly into the mesothelioma cells.
How it works is as follows. MV-NIS (NIS refers to the inserted gene) codes for the thyroidal sodium iodide symporter, the mechanism that concentrates radioactive iodine into infected cells. Using the radioactive iodine, researchers can then conduct imaging studies (SPECT/CT) to follow the virus in treated patients. If they see evidence of substantial radioiodine uptake by the mesothelioma cells on these imaging studies, they can then administer a more toxic version of the radioactive iodine to destroy mesothelioma tumors.
Minnesota Partnership Launches Study
After the measles virus was shown to kill cancer cells in the lab, researchers decided to test it in animal models. They found that in mice infected with mesothelioma, one injection of the virus doubled their life span in comparison to those mice that were not given the virus. Some of the mice even appeared to be cured.
As a result, Phase I clinical trials are beginning, in which 12 to 36 patients will be divided into two groups. Participants in one of the groups will receive MV-NIS injections into their chest cavities through catheters that will also drain excess fluid caused by mesothelioma from around their lungs. Researchers hope the mesothelioma tumors will shrink significantly. At the start scientists will use lower amounts of the measles virus as they test for toxicity and adjust the dosage for effectiveness.
If it succeeds in clinical trials, the engineered measles virus could be combined with chemotherapy. This would suppress the body’s immune response against the virus, giving it more time to work on cancer cells before the immune system shuts it down.
The initial research for this study was funded by a grant from the Minnesota Partnership for Biotechnology and Medical Genomics.
A much larger international clinical trial is slated to study the drug pazopanib, a tablet sold by GlaxoSmithKline under the trade name Votrient. It will likely include more than 500 patients over three years.
Pazopanib is currently approved by the FDA to treat kidney cancer. It is an angiogenesis drug, meaning it targets the growth of new blood vessels in cancerous tissue by blocking nutrients and oxygen. Researchers discovered the drug’s potential as a treatment when they added it to mesothelioma cells. They noticed it was very effective at killing the cells. At the time, researchers were testing pazopanib for efficacy against all tumor types.
The results of a small human study were encouraging. The median survival for a patient with pleural mesothelioma is 9 to 12 months. According to researchers, pazopanib improved survival times in patients by six months.
Unlike traditional chemotherapy, pazopanib uses a targeted approach to kill cancer cells. Instead of killing all rapidly growing and dividing cells, it targets cancer cells that rapidly form new blood vessels. Because this approach targets the cancer cells alone, instead of also targeting otherwise healthy body cells, it leads to fewer side effects.
Based on the drug’s potential, the National Cancer Institute has funded a Phase II clinical trial for patients with pleural mesothelioma, which will be led by the Mayo Clinic.
To monitor how well pazopanib is working, researchers will use CT scans of the chest to enable them to see tumors from different angles. Researchers will perform the CT scans every six weeks.
Participation in the study is being offered to patients who have not been treated with chemotherapy. Study participants will be randomly divided into two groups. One group will receive 800 milligrams of pazopanib once a day, while a control group will receive standard chemotherapy.
According to researchers, the goal is to change the standard of care for mesothelioma treatment from chemotherapy to pazopanib, which they say can improve survival by six months, as well as improve quality of life.
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