In a proof of principle clinical trial, Mayo Clinic researchers have demonstrated that virotherapy — destroying cancer with a virus that infects and kills cancer cells but spares normal tissues — can be effective against the deadly cancer multiple myeloma. …
Oncolytic virotherapy — using re-engineered viruses to fight cancer — has a history dating back to the 1950s. Thousands of cancer patients have been treated with oncolytic viruses from many different virus families (herpes viruses, pox viruses, common cold viruses, etc.). However, this study provides the first well-documented case of a patient with disseminated cancer having a complete remission at all disease sites after virus administration.
Lead researcher Stephen Russell said he and his team had engineered the virus to make it more suitable for cancer therapy. And, after just one dose of it, Erholtz’s cancer went into remission. She has been completely cleared of the disease, Russell wrote in Mayo Clinic Proceedings. Though, in this trial, the treatments were successful on only one of the two patients.
Russell said the trial taught the medical researchers two things: “No. 1, you need a really big dose and No. 2, the patient needs to not have an antibody to the virus.”
The research, published online Wednesday in the journal Mayo Clinic Proceedings, represents a “benchmark to strive for and improve upon,” according to an accompanying editorial by Dr. John C. Bell of the Centre for terInnovative Cancer Research in Ottawa.
“Without trying to hype it too much, it is a very significant discovery,” Bell said in an interview.
The next step is a bigger trial to see if the measles blitzkrieg works in a larger number of patients — a trial that Mayo expects to launch no later than September.
Researchers have known for decades that viruses can be used to destroy cancer. They bind to tumors and use them as hosts to replicate their own genetic material; the cancer cells eventually explode and release the virus. Antiviral vaccines that have been rendered safe can produce the same effects and can also be modified to carry radioactive molecules to help destroy cancer cells without causing widespread damage to healthy cells around the tumors. The body’s immune system then attacks any remaining cancer that carries remnants of the vaccine’s genetic imprint.
Researchers worldwide are working with a variety of cancer-killing viruses, including herpes and poxvirus, and they have produced long-lasting cures in rodent studies, Bell noted in his editorial. “Many have been tried in humans but no one has shown this type of systemic activity [seen in the Mayo study],” he said.
The Mayo research could also help solve a related puzzle. Researchers have suspected for some time that there is a threshold level of virus that is required to defeat the defense mechanisms in cancerous tumors, Bell said, and the Mayo study helps set the bar.
In addition, various viruses show an affinity for particular organs, Russell said. Pneumonia and influenza, for example, damage the lungs. Hepatitis damages the liver.
“We have a virus that can do that selectively to a tumor without at the same time causing damage to normal tissues in the body,” Russell said.
The strain that Russell used was isolated in 1954 from the throat of an 11-year-old boy named David Edmonston and has been used to safely make all of the measles vaccines used in the West, he said. The virus treats multiple myeloma tumors as food and turns them into machines to make copies of itself.
Most people have been inoculated with the vaccine, rendering it vulnerable to their immune systems. But patients with multiple myeloma often have suppressed immune systems, which can allow the virus to do its work.
The normal dose of vaccine contains 10,000 infectious units of the measles virus, Russell said. Mayo started out giving patients 1 million infectious units and gradually cranked up the dosage — but it didn’t work until Erholtz and another patient were injected with 100 billion infectious units, he said.
While the treatment worked in Erholtz, whose tumors were primarily in her bone marrow, the results weren’t sustained in the second patient, whose tumors were largely confined to her leg muscles. Russell said researchers need to study how the nature of the tumor affects the lethality of the virus.
“I think if we had been able to give bigger dose, we might have got a better outcome in that second patient,” he said.
But at least for now, there’s no second chance. Once the vaccine has been delivered, the body’s immune system will recognize it and attack it. Russell said breaking down the immune system before the treatment will be part of another upcoming clinical trial.
Researchers also may be able to bypass the immune system by taking a patient’s cells and converting them into Trojan horses. The virus is loaded into the cells, and they are injected back into the bloodstream. “That way it doesn’t get destroyed before it reaches its target,” Russell said.
Close to success
At the James Cancer Hospital and Solove Research Institute in Ohio, Dr. Tanios Bekaii-Saab is working on a study to treat pancreatic cancer using Reolysin, a proprietary variant of the virus that causes the common cold.
Researchers, he said, have two primary approaches: Inject the virus directly into tumors to get past their defenses or inject it into the bloodstream and hope it will seek out tumors and overwhelm them, as was done in the Mayo study.
Saab said he expects one of these virus “platforms” is likely to become standard treatment for a cancer such as myeloma or pancreatic cancer within three to four years.
After reading a draft of the Mayo study, Saab called it “an incredibly innovative way to actually attack the cancer and perhaps even offer a better chance at complete remission,” especially in combination with radioactive molecules and immune system therapy.
He cautioned that the study still must be confirmed in large randomized clinical trials — the point where many hopes get dashed.
“Unless we get to the third stage of development, we are only cautiously optimistic,” Saab said.
Other such trials are going on across the country, such as the NeuVax clinical trial for patients at risk for breast cancer recurrence. Another one, which is run by the Providence Cancer Center, will use dangerous bacteria instead of viruses to treat glioblastoma, a type of common brain cancer, according to Medical Daily.