Not too long ago, scientists injected 50-year-old cancer patient Stacy Erholtz with a special strain of the measles virus. After suffering through a barrage of symptoms that included a severe headache, vomiting, shaking, and a fever upwards of 105 degrees, something remarkable happened. In a matter of weeks, the tumors that were taking over her body shrank to the point where they were no longer detectable. That one dose, enough to inoculate 10 million people, turned out to be just enough to overwhelm her disease.
Another patient participating in the study, also battling myeloma, a cancer of the blood, experienced some improvement as well, though not nearly as dramatic. The Erholtz case stands out for demonstrating that, for the first time, a virus can be used to beat back cancer to the point where doctors declared her to be in complete remission. “The main thrust of this is that we’ve proven that this treatment is beneficial,” said hematologist Stephen Russell of the Mayo Clinic, who led the trial. “We have seen it in mice and now we’re seeing it in humans, so it gives us a lot of confidence that someday we can develop a single shot cure that will completely wipe out a patient’s cancer.”
But not long after word of Erholtz’s case got out, skeptics began offering up their own tempered-down version of where these kind of interventions stand. In a blog post titled “Could measles cure cancer? Uh, not exactly,” Cancer Research UK, a leading independent research institution, emphasized that although the patient had a “strong response” to the treatment, the cancer did eventually come back nine months later. In an editorial, Ars Technica editor John Timmer, a former molecular biologist, pointed out that earlier trials also reported results that, at the time, “looked very promising,” but haven’t — as of yet — yielded any viable treatments. “It’s important to note that a short-term remission in one of the two patients who are described here doesn’t come anywhere close to being a general cure for this type of cancer,” he wrote.
As some have noted, the tendency of some cancers to regress following a viral infection had been observed by practitioners for some time now, as far back as the beginning of the twentieth century. In the 1950s, investigators experimenting with cancer-infecting or “oncolytic” viruses were even able to, in some instances, reverse the growth of certain tumors such as Burkitt lymphoma, Hodgkin lymphoma and cervical cancer. Back then, they simply tested naturally-evolved strains that were found to be effective against specific types of cancer. The herpes virus, for example, is particularly well-suited for treating cancers of the brain since it generally latches on to nerve cells. Unfortunately, this initial foray into virotherapy was largely abandoned partly because there wasn’t a way to infect the targeted sites in a controlled manner.
It’s only with recent advances in bioengineering techniques that the field has undergone a sudden resurgence. California-based Amgen, the world’s largest independent biotech firm, has made steady progress on a modified version of the herpes virus (T-Vec) that was shown to be effective in shrinking skin tumors (melanoma). And in 2005, a modified strain of H101, which attacks cancer of the head and neck, was given regulatory approval by China’s State Food and Drug Administration to become the first commercially-available oncolytic-based treatment. This was after a clinical trial had shown that injections reduced tumors in nearly a third of patients compared to a control group. “What makes viruses an especially effective weapon against cancer is that it will change and adapt to whatever you are growing it on,” Russell explained. “And they became very good at attacking cancer cells, but at the same time lose their ability to attack normal cells.”
In Erholtz’s case, Russell and his team were able to identify a strain of the measles virus, used in vaccines, that happened to latch on to a protein receptor frequently found along the surface of myeloma cells. The virus also carried with it an extra gene, taken from the thyroid gland, that instructs proteins to absorb radioactive iodine from the bloodstream and import it into cells as infection spreads. After injecting the virus directly into the tumors, and then the iodine, researchers were then able to use an imaging device called SPECT-CT to track the rapid demise of each cancer cell as well as determine the cause. With this, they discovered that the virus was indeed responsible for killing the lion’s share of cancer cells, just prior to an immune response that kicked in later to mop up the remaining remnants.
Russell surmises that if her immune system hadn’t eradicated the virus before it was able to infect every cancerous cell, the treatment could have finished off the tumors entirely. “It’s sort of a race,” Russell explained. “To give the virus enough of a head start in eliminating the tumor before the immune system goes into action, we need a higher dose — though not too much because there’s a level of toxicity that’s potentially dangerous to the patient. It’s going to be a complex therapy and we’re going to strike the right balance.”
Another challenge is that oncolytic virotherapy tends to be literally a one-shot deal — at least for now. That’s because once treatment has been administered, the immune system develops anti-bodies to quickly recognize and fend off the virus. The current method also renders it ineffective for those who have already been vaccinated. For this, Russell already has at least a couple workarounds in mind. One solution, which he calls the “Trojan horse” strategy, involves masking the virus’s entry by bundling it inside a cell derived from the patient’s own DNA to avoid automatically triggering the body’s defenses. Another approach is to combine virotherapy with immunosuppressant medications as a way of buying the virus enough time to infect as many cancerous cells as possible.
Russell says that a phase II trial, scheduled for September, and which involves more patients as well as higher doses, is already in the planning stages. In the long term, Russell hopes to produce enough data to develop a treatment that meets the Food and Drug Administration’s criteria for both effectiveness and safety. His team is also looking into scaling up the process of manufacturing viruses to where labs can reliably produce a sufficient amount of infectious units to deal a real death blow to cancer cells, thus preventing them from coming back.
“We can easily take out tumors in mice, but the hard part is that humans weigh 3,000 times more,” he said. “To make a high enough dose, especially for those with later stage cancers, is going to be a huge undertaking.”