Harnessing herpes virus to beat deadly brain cancer

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TUESDAY, Feb. 8, 2022 (HealthDay News) — A genetically modified herpes virus appears to deliver a “one-two punch” to the rare and deadly form of brain cancer who killed US Senator John McCain, new findings show.

glioblastoma brain tumors they are a cancer nightmare, with an average survival of 12 to 15 months from initial diagnosis and four to six months after recurrence, the researchers say. McCain he died in August 2018, a year after doctors discovered he had aggressive cancer.

“Despite 50 to 60 years of research and advances in surgery, chemotherapy Y radiation, we haven’t pushed the needle very far in terms of survival,” said lead researcher Dr. James Markert, chair of neurosurgery at the University of Alabama Heersink School of Medicine at Birmingham. “Only 5% to 10% % of patients live more than five years. It’s almost universally fatal.”

But a fight against experimental cancer herpes simplex virus called G207 has shown promise in fighting glioblastomaand an article published on February 1 in Cancer Clinical Research provides a better idea of ​​how.

G207 is known to directly attack and kill brain tumor cells, Markert said.

“There is something different about the defense of tumor cells against viruses, such that the DNA changes that prevented the virus from being infectious in normal human cells were not present in tumor cells,” he said. “As a result, the virus became selective in infecting and killing tumor cells.”

Now it turns out the virus has another trick up its sleeve: It robs glioblastoma of its ability to evade detection by the immune system. Highlighted by the virus, brain cancer is attacked by the body’s natural defenses.

“It became apparent to us that there really was a double whammy,” Markert said. “The virus invoked an immune response against the tumor as a secondary type of antitumor response produced by the infection.”

Results of a phase 1B clinical trial involving six adult glioblastoma patients with recurrent or progressive tumors provided Markert and his team with a new understanding of how the modified herpesvirus attacks cancer.

In the trial, patients had their glioblastomas surgically removed and then most underwent radiation and chemotherapy.

The herpes virus was then injected directly into the site of their tumors.

A few days after treatment with the virus, the researchers extracted genetic material from the treated tumors in order to better understand what happens inside the cancer when G207 attacks.

Untreated glioblastoma cells usually do not contain genetic evidence of any immune response. “The tumor actually produces a number of factors to discourage the immune system from attacking it. It’s trying to act like a sneaky invader as best it can,” Markert said.

But after G207 treatment, the tumors “overflow with immune cells,” he said. Viral infection appears to produce a “danger signal” that directs the immune system’s attention to the cancer.

“By studying genes associated with survival, [the researchers] found that it was related to the activation of immune cells, activating the body’s immune system to help fight cancer,” said Dr. William Cance, chief medical and scientific officer of the American Cancer Society. “It gives us hope that that we can turn the immune system against these deadly brain tumors.

Further analysis revealed about 500 genes that are significantly associated with patient survival after G207 treatment, and about half are related to immune response, Markert said.

“Hopefully the information is going to predict who are going to be the people who are going to do really well and who might need another treatment,” he said.

Five ongoing clinical trials are using genetically modified herpesviruses to target tumors of the brain and spinal cord, the researchers said.

Trials have shown that herpes virus treatment produces overall, but not uniform, improvements in overall survival, the researchers noted. For example, two of the 36 glioblastoma patients treated with G207 in phase 1 trials had long-term survival of more than five and seven years.

In the most recent trial, the G207 virus kept four of 11 pediatric patients alive 18 months after treatment, Markert noted. Those results were published last spring in the New England Journal of Medicine.

“It turns out that children do even better with the virus,” Markert said. “We think it’s because their immune systems may be stronger and their tumors are a little bit more sensitive to the virus.”

Plans are underway to start a phase 2 study through a pediatric brain tumor consortium, Markert said.

“The frustrating thing about glioblastoma is that there are very limited therapies that have very limited efficacy. We need novel approaches to treat brain tumors like this,” said Cance, who was not part of the new study.

He said the new document provides a clearer explanation of how the virus therapy works and who could best benefit from it.

“Hopefully, as they learn what predicts response, they’ll be able to be more selective about which patients get it,” Cance said.

Since glioblastoma is a rare disease, Markert said the researchers hope to persuade the US Food and Drug Administration to allow accelerated approval of G207.

This would not be the first FDA-approved herpes cancer treatment, Markert noted. In 2015, the agency approved Imlygic, a treatment produced by Amgen for melanoma which also uses a modified herpes simplex virus.

“It turns out that melanoma responds very well to immunotherapies, so it’s quite logical that the virus would help get through things and make a good immune response against a cancer that’s already susceptible to these kinds of things,” Markert said. “Glioblastoma is much more of a tough nut to crack.”

More information

The American Brain Tumor Association has more about glioblastoma.

SOURCES: James Markert, MD, MPH, chairman, neurosurgery, Heersink School of Medicine, University of Alabama at Birmingham; William Cance, MD, medical and scientific director of the American Cancer Society; Cancer Clinical ResearchFebruary 1, 2022

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