Uncovering how viruses can kill cancer.
E. Antonio Chiocca, MD, PhD
Brigham and Women’s Hospital
“Cancer is not a defined or fixed entity,” says E. Antonio Chiocca, MD, PhD, the neurosurgeon-in-chief and chair of the Department of Neurosurgery at Brigham and Women’s Hospital. “Cancer evolves, grows and changes over time, which means effective treatments need to be able to respond in kind. They cannot be stationary or limited in scope. They must be able to adapt to the changing landscape of cancer.”
It is at this moving target that Dr. Chiocca has been taking aim since 1991, with a focus on one of the toughest-to-treat brain tumors: glioblastoma. According to the National Brain Tumor Society, glioblastoma is diagnosed in approximately 15,000 people in the U.S. each year, the average survival is 8 months, and the 5-year survival rate is less than 7%.
Dr. Chiocca has always been confident that oncolytic viruses can eliminate glioblastoma cells. Now, he knows how.
“We used to think of oncolytic viruses as an infection that could kill cancer cells,” Dr. Chiocca says. “Now we think of them as a match that lights the fuse: bringing the immune system to kill the tumor.
“Oncolytic viruses, more so than any other therapy out there, can get immune cells into these solid tumors to fight the cancer.”
Oncolytic viruses team with the immune system.
Dr. Chiocca’s strategy combines several elements, beginning with harnessing the virus’ power to infect cells. Oncolytic viruses are modified versions of viruses engineered to infect cancer cells while ignoring healthy cells. The viruses cause the cancer cells to break apart and die.
This initial step is what many scientists focused on when they first began developing oncolytic viruses to fight cancers such as glioblastoma. However, they discovered the engineered viruses also can activate the patient’s immune system to join the fight.
“Oncolytic viruses are really good at causing an inflamed environment around the tumor, which alerts the immune system,” Dr. Chiocca says. “Once you inject the virus, you get an amazing amount of T cells and other immune cells migrating to the tumor – much more than with other therapies. We think this is a way to stimulate the immune system to begin attacking the tumor.”
ACGT-funded research guided Dr. Chiocca.
Thanks to support from Alliance for Cancer Gene Therapy (ACGT), Dr. Chiocca has already shown the potential of oncolytic viruses to fight glioblastoma. In 2007, ACGT awarded him grant funding to test the safety of this innovative approach. This led to a phase one clinical trial in which 41 patients were treated with Dr. Chiocca’s virus. Early results of the trial were published in 2023 with several patients achieving significant increased survival.
The engineered virus in the clinical trial is especially beneficial for people with glioblastoma whose immune systems have pre-existing antibodies for the virus, which means their immune systems respond quickly to the presence of the virus. Participants in the trial with pre-existing antibodies have had an average survival of 14.2 months, an improvement from the average survival of 8 months associated with glioblastoma. The phase 1 trial continues to recruit patients and more information is available on clinicaltrials.gov.
“This trial is what changed my mind and other people’s minds on how these viruses work,” Dr. Chiocca says. “At the time I got funding from ACGT in 2007, we were just trying to make a targeted virus that would infect cells. What we found from the clinical trial is quite a bit of tumor infiltration of T cells (a type of immune cell) into these tumors after injecting the virus. We also found that the number of T cells coming in directly correlated with survival.”
Dr. Chiocca continues to evolve his approach to treating glioblastoma and is preparing for a new trial in which patients will recieve six serial injections of the oncolytic virus instead of just one. Having demonstrated the safety of one viral injection, he is proceeding to test the safety and efficacy of up to six injections over four months, which, like multiple rounds of vaccination, may increase the effectiveness of the therapy.
Second grant awarded to Dr. Chiocca.
In 2023, Dr. Chiocca received a second grant from ACGT to continue developing a “next-generation” oncolytic virus for patients with glioblastoma. The funding from ACGT will help Dr. Chiocca run pre-clinical studies required by the FDA to show that this modified oncolytic virus is safe to use in humans, which hopefully will lead to another clinical trial.
“The phase 1 clinical trial that came from the first ACGT grant shows that this approach should be further developed,” he says. “As you continue to work in science, you come up with new ideas. This new virus has modifications, such as replacing one of the genes in the virus. This could help the virus infect tumor cells more effectively and prevent some side effects.”
“We used to think of oncolytic viruses as an infection that could kill cancer cells. Now we think of them as a match that lights the fuse: bringing the immune system to kill the tumor.”