Medical Edge Newspaper Column

Can A Mutant Measles Virus Threaten Populations?

February 29, 2008
Dear Mayo Clinic:
The recent film "I am Legend" is about a genetically altered virus that is supposed to cure cancer but instead kills most of the people on the planet. I read that the measles virus is being tested as a cure for cancer. Is it safe?

Answer:
The film you mention, based on the 1954 science fiction novel by Richard Matheson, plays on our anxiety about the emergence and spread of lethal viruses. In the movie, a genetically engineered measles virus is used successfully to treat cancer. But it then evolves to become a deadly pathogen that spreads uncontrollably and causes a rabies-like illness.

Research using a genetically engineered measles virus as an experimental cancer therapy has been under way for several years. The altered virus is derived from the measles vaccine, a weakened strain of measles that has been effectively controlling the measles virus for decades.

The vaccine has remained effective because the measles virus itself is very stable. Over thousands of years, it has not evolved to cause anything worse than measles. In the same way, the measles vaccine has never changed to a measles-causing (wild type) strain. Indeed, it was precisely because of its extraordinary safety features that measles was chosen for this cancer research from more than 2000 alternate viral species.

The worst-case scenario for the use of a genetically engineered measles virus in cancer treatment is that it might revert to the wild type measles strain and cause measles in the treated patient. However, because the engineered measles viruses are genetically very similar to the measles vaccine, this is highly unlikely. But what if the virus did mutate in the treated cancer patient, becoming once again capable of causing measles?

First, while measles is not a pleasant illness, it has a very low mortality; less than one out of every 1000 people infected with the virus in the United States is likely to die from complications related to measles. Second, because of childhood measles vaccination, which gives lifelong protection, most of the world's population is currently measles-immune. This means that, even if the anticancer virus could revert back to become a measles-causing strain (and we do not believe it can), the vast majority of people would be immune and infection could not spread.

Measles is therefore about the safest virus that could possibly be selected for the purpose of treating cancer. But if the patient has pre-existing antiviral immunity, can such a virus be an effective cancer therapy? This is an important question since a therapeutic measles virus administered into the vein of a measles-immune cancer patient would most likely be neutralized before it could ever reach the cancer.

Current research uses two approaches. One is to inject the virus directly into the site of tumor growth. The second is to administer the virus into a vein in cancer patients who are lacking anti-measles immunity, either because we give them drugs that momentarily suppress their antiviral immunity, or because their cancer naturally suppresses their antiviral immunity.

In preclinical trials, the genetically engineered measles virus (measles virotherapy) was highly effective. Then, after federal and institutional committees reviewed the research to ensure that the patient and community safety were fully addressed, clinical trials began. These trials, involving patients with ovarian cancer, brain cancer and multiple myeloma, are showing early promise and more are planned. Our hope is that, in the near future, measles virotherapy will prove to be an additional weapon in the fight against cancer.

— Stephen Russell, M.D., Ph.D., Molecular Medicine Program, Mayo Clinic, Rochester, Minn.