MAGIC BULLET

05.15.14

Are Viruses the Next Cure for Cancer?

Giant doses of a genetically modified measles vaccine cured two of blood cancer at the Mayo Clinic this week. Why the magic remedy must be met with caution.

The unlikely strategy of using a live virus to treat cancer took yet another step forward this week with the news that scientists at the Mayo Clinic had treated two adults with the blood cancer, multiple myeloma, by injecting them with mega-doses of genetically modified measles virus.

Both patients had failed all other available therapies; with the new “oncolytic virus” treatment, each responded and one remains in remission nine months later.

In this study, the patients—neither with existing antibody to measles virus—received enormous doses of live measles virus infused directly into their vein—not given as a shot like a vaccine. Both became feverish and ill with the infusion, as expected, and both recovered. The measles virus was derived from the strain used in routine measles vaccine but had been carefully altered by scientists to enhance its tumor killing effects. It was still, however, a measles virus, capable of giving a person a measles-like illness. The choice of measles for the cancer was quite deliberate—this virus is known to seek out and attack a type of white blood cell that myeloma arises from. The investigators simply harnessed measles virus’ natural born killer tendency.

As the investigators noted, the patients’ lack of immunity was critical to the success of this study. Most people—at least 95 percent of adults—have pre-existing antibody to measles. This is a good thing to assure they will not develop measles but would be extremely problematic for measles oncolytic therapy—the patient’s own antibody would kill off the killer measles before it could reach the cancer cell. Thus a major problem with all oncolytic virus treatment—the patient’s immune system, which has its own seek and destroy mission—was circumvented in the Mayo trial.

For these patients, it is unclear how long the treatment benefit will last. With a disease like myeloma, cure is unusual. A very long remission and stability is considered a substantial success. But using the muscle power of viruses and other infections is an exciting new frontier, albeit one based on rather old observations.

Scientists have been fascinated by the approach for years. One of the first possible demonstrations of effect was with the use, more than 100 years ago, of something called Coley’s toxin, a mish-mosh of killed bacteria and other proteins that was injected near and directly into solid tumors.

The news that measles virus might have benefit and that a patient is doing well, for now, is credible and exciting—but we are still miles and miles away from this sort of approach becoming routine for cancer.

Although the approach engendered substantial excitement, Coley’s toxins were never proven to be beneficial. Many small trials were performed—some showed effectiveness, others did not. In 1963, more than 70 years after it was introduced, the FDA determined that the product could only be given in the context of clinical trials. The strategy, though, captured the imagination of scientists worldwide and gave birth to the field of immunotherapy, which is extremely hot today.

The next well-publicized study using infection to kill cancer took place in the 1950s. West Nile virus, then considered a harmless infection, was given to more than 100 patients at what is now Memorial Sloan Kettering Cancer Center. A scientist, Dr. Chester Southam, had noticed that West Nile, discovered in the late 1930s, had tumor-shrinking properties in various experiments and so offered the treatment to patients without other cancer-treatment options as part of a clinical trial.

A few patients responded, particularly those with lymphoma and one newspaper ran an excited headline, Deep Cancers Temporarily Shrunk by Rare Nerve Virus From Africa, trumpeting the breakthrough.

The problem though was a spate of unexpected side effects—about 10 percent of the patients got drowsy and confused—presumably developing the disease we now recognize as West Nile encephalitis. This unexpected finding, as well as the mediocre antitumor effect, led to the end of the trial.

But once again, the science of the approach was compelling. A generation later, a better understanding of viruses and their ability to enter and destroy certain cells made “oncolytic virus” treatment again of interest to scientists. Herpes virus, adenovirus and many others have been studied against a wide variety of cancers; many trials are ongoing. The enthusiasm is such that even the oldest of all vaccines—vaccinia, the ur-shot used to prevent small pox—has been called into action with interesting preliminary results.

Though an area of very active investigation, no one is certain why this approach works. Some think that the virus has the ability to goose up a person’s immune system in a non-specific way, and that with a heightened and more sharply tuned immune repertoire, cancer cells are attacked and killed more or less accidentally.

Others point to the unique properties of viruses to enter cells and kill them; they posit that the task is only to find the right virus for each tumor, as was done with the current measles versus myeloma study. They envision a group of stealth killers each with a seek-and-destroy mission killing cancer “naturally.” And bonus—with some viruses, such as herpes, once the task is done, the virus itself can be killed off using routinely available anti-herpes antivirals.

The news that measles virus might have benefit and that a patient is doing well, for now, is credible and exciting—but we are still miles and miles away from this sort of approach becoming routine for cancer. Once again we should walk the fine line between soaring hope and miserly caution and give scientists the time (and funding) to complete thoughtful, well-designed studies.