An experimental gene therapy that uses a modified herpes virus shows promise as a brain cancer treatment, according to new research. The Phase I study found evidence that the virus could safely induce an immune response that attacked the often-fatal cancer. It also seemed to extend the length of survival in those who had pre-existing antibodies to the virus.
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Brain cancers are some of the hardest to successfully treat, particularly glioblastomas (GBM), the most commonly diagnosed form. GBMs are incredibly aggressive and can quickly spread to other parts of the brain, making total surgical removal next to impossible. Existing radiation and chemotherapy treatments usually fail to finish off the cancer, and GBM is currently considered incurable, with the average length of survival hovering around eight months, according to the National Brain Tumor Society.
But researchers from Brigham and Women’s Hospital and elsewhere believe that they may have found a new way to attack these cancers, using a ubiquitous microbial foe of ours. Their therapy relies on a genetically modified herpes simplex I virus, a germ that usually causes cold sores and, less commonly, genital herpes.
“A reason for failure is that GBM is able to escape your own immune cells that actively fight against the tumor,” study author E. Antonio Chiocca, chair of the department of neurosurgery at Brigham and Women’s, told Gizmodo in an email. “We engineered in our laboratories a tumor selective biologic agent (based on the cold sore virus, herpes simplex virus type 1) to inject into the GBM of patients with the goal to see if we could reshape the GBM to become less able to escape the patient’s immune cells.”
There are other cancer-killing treatments based on the herpes virus, either in development or already approved for specific cancers like melanoma. The team’s creation, dubbed CAN-3110, is a bit different from other therapeutic versions since it still contains a gene that helps the wild herpes virus cause disease in humans, called ICP34.5. Chiocca and his team believe that ICP34.5 is needed to provoke a strong enough immune response to brain cancer cells, but they’ve tried to genetically program CAN-3110 to not attack healthy cells.
In their latest research, published Wednesday in Nature, the therapy appears to be off to a promising start.
The team gave 41 patients with high grade brain and spinal cord tumors, including 32 people with recurrent GBM, a single dose of CAN-3110. Phase I trials are mainly intended to confirm the short-term safety of an experimental treatment, and the treatment did appear to be generally well-tolerated (two patients did experience seizure possibly linked to it). About two-thirds of patients had existing antibodies to the herpes virus, and in these patients, the researchers also found evidence that the treatment boosted the immune system’s response to the cancer. Importantly, the median survival of these patients was around 14 months, compared to just under 8 months for those without previous exposure to herpes.
“Unlike other therapies so far, we have been able to show that one single timepoint administration of CAN-3110 is sufficient to activate the patient’s own immune cells to traffic and fight off the cancer and we show that this links to survival responses,” Chiocca said.
It will take much more research to confirm whether CAN-3110 could be a viable treatment for brain cancer, including in people without past herpes exposure (that said, a majority of people worldwide do carry antibodies to it). CAN-3110 has since been licensed for further development by the company Candel Therapeutics. And thanks to a funding grant from the research foundation Break Through Cancer, Chiocca and his team are already working on their next study, which will hopefully determine the optimal dosing of the therapy.
“We are now doing multiple timepoint injections of CAN-3110 into patients to longitudinally treat the cancer over four months, as well as sampling the GBM being treated to ensure that these immunoactivating programs remain operative,” he told Gizmodo.
