Genetically modified HERPES virus injected directly into the skull of children with terminal brain tumors ‘doubles their life expectancy,’ new trial shows
- A new trial at the University of Alabama Birmingham tested oncolytic herpes viruses on children with the deadliest forms of pediatric brain tumors
- The virus is genetically modified to only infect and kill tumor cells, and spurs a strong response from the immune system to help fight the cancer
- Eleven of the 12 patients showed signs that the treatment was working and the median survival was one year, more than double the expected survival rate
- One of the patients, Jake Kestler, underwent the treatment at age 12, and lived for a year and four months after, when expected survival was just six months
- Early results suggest the virus treatment is helping, and doctors are now planning to verify them in a larger study
For decades, one of the deadliest kinds of pediatric tumors has eluded science’s best tools and had even been considered untreatable.
But researchers have made progress with an unusual treatment that involves injecting a genetically modified herpes virus into children’s brains to infect their tumors, which spurs the immune system to attack.
At least a dozen children have undergone this treatment and lived twice as long as other patients have in the past, doctors reported on Saturday at the virtual American Association for Cancer Research conference.
Although most of them eventually died of their disease, a few are alive and well several years after treatment — something virtually unheard of in this situation.
‘This is the first step, a critical step,’ said study leader Dr Gregory Friedman, a childhood cancer specialist at the University of Alabama at Birmingham (UAB).
‘The key findings thus far are that the approach is safe and well tolerable, and the preliminary evidence of efficacy is promising.’
Jake Kestler (center) who was diagnosed with brain cancer was one of the patients who underwent new trial at the University of Alabama Birmingham testing oncolytic herpes viruses. Pictured: Kestler with his parents, Gallite and Josh, and his sister, Lily, in 2016
The virus is genetically modified to only infect and kill tumor cells, and spurs a strong response from the immune system to help fight the cancer. Pictured: MRI images show a brain tumor before the treatment (on left, light-colored area) and after the treatment (right)
Eleven of the 12 patients showed signs that the treatment was working and the median survival was one year, more than double the expected survival rate. Pictured: Jake (center) before his cancer diagnosis
The study, published in The New England Journal of Medicine, focused on children who have been diagnosed with glioma, tumors which begins in the glial cells that surround nerve cells and help them function.
Symptoms include headache, memory loss, nausea, vomiting, difficulty with balance and vision problems.
Gliomas accounts for between eight and 10 percent of childhood brain tumors.
Although treatment can vary based on the size, type and location of the tumor, standard options include surgery, radiation, chemotherapy and targeted drug therapy.
However, these tumors often recur and, when that occurs, survival averages just under six months.
What’s more, the share of children who are alive more than five years after their diagnosis is just 10 percent.
Oncolytic herpes viruses are derived from the standard herpes virus that causes sores around the mouth and lips.
Scientists genetically modify the virus so that it only infects and kills cancer cells.
Through a tiny tube called a catheter, the virus is injected directly into the tumor.
It then multiples, which kills the initial tumors cells.
The virus can then continue spreading to other tumor cells.
In addition, the virus spurs a strong immune system response so the body can recognize the cancer again and also help fight it off.
A recent trial at the University of Alabama Birmingham found that survival was just over one year, more than double the expected survival rate.
In such cases, the immune system has lost the ability to recognize and attack the cancer, so scientists at UAB have been seeking ways to make the tumor a fresh target.
They turned to G207, which derived from the herpes virus that causes cold sores – and also spurs a strong immune system response.
The treatment, called oncolytic herpes viruses, was first developed in the 1990s by a team at Massachusetts General Hospital.
For the new study, a suburban Philadelphia company called Treovir developed a treatment by genetically modifying the virus so it would infect only cancer cells.
When injected through tiny tubes inserted in the tumors, the modified herpes virus enters tumor cells and makes multiple copies of itself.
The virus then kills the initial cells and then releases new particles to hunt other tumor cells.
Additionally, the virus induces the immune system to mount a strong response so it begins to recognize the cancer again.
Doctors gave the altered virus to 12 patients between ages seven to 18 whose cancer had worsened after usual treatments.
Half of the patients received just the virus and the other half got the virus plus one dose of radiation, which is designed to help the virus spread throughout the tumor.
During the trial, 11 of the 12 patients showed signs that that the treatment was working.
Median survival was just over one year, which is more than double the expected survival rate of children with high-grade gliomas.
As of last June, the cutoff for analyzing these results, 36 percent, or four patients, were still alive at least 18 months after treatment.
Tests also showed high levels of specialized immune system cells in their tumors, suggesting the treatment had recruited the help needed from the body to attack the disease.
The treatment also increases the number of activated cells immune cells to help fight the cancer. Pictured: The number of cells before the treatment (left, in black) and after the treatment (right, in black)
Early results suggest the virus treatment is helping, and doctors are now planning to verify them in a larger study. Pictured: Study leader Dr Gregory Friedman, a childhood cancer specialist, looks through a microscope at a laboratory in Birmingham, Alabama, August 2019
No serious safety issues were seen, though there were several procedure-related complications and mild side effects including nausea, vomiting, diarrhea and fatigue.
One of the children in the trial was Jake Kestler, of Livingston, New Jersey, who was diagnosed with brain cancer in 2016.
Jake (pictured) underwent the treatment at age 12, and lived for a year and four months after, when expected survival was just six months
After all other treatments failed, he was enrolled in the clinical trial at age 12.
‘It went very well. He lived for a year and four months after that,’ his father, Josh Kestler, a financial services executive, told the Associated Press.
It was long enough for Jake to celebrate his bar mitzvah, travel with his family to Hawaii and witness the birth of his baby brother.
Jake died on April 11, 2019, but ‘we have no regrets whatsoever’ about trying the treatment, said Kestler, who with his wife has started a foundation, Trail Blazers for Kids, to further research.
‘It’s a devastating disease for these patients and their families,’ said Dr Antoni Ribas, a cancer specialist at the University of California, Los Angeles, and president of the group holding the conference.
He says that while the early results suggest the virus treatment is helping, they need to be verified in a larger study, which doctors are currently planning.
Friedman said studies are continuing in adults as well, and plans are in the works for other types of childhood brain tumors.
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