A therapy combining cell-killing and immune-stimulating drugs is safe and effective in extending survival for patients with gliomas, a highly aggressive form of brain cancer, according to a study published in The Lancet Oncology journal.

Given gliomas' poor prognosis and limited response to treatments like chemotherapy and radiation, the team looked to using the protein Flt3L to recruit immune cells, typically absent from the brain. These immune cells are required to kick start a more effective cancer immune response.

"Being able to move a novel therapy from bench to bedside in such a streamlined fashion is exciting, and represents a tour-de-force in translational medicine," said Oren Sagher, a professor of neurosurgery at the University of Michigan (U-M), US.

The study focused on two types of genetic therapies in high-grade gliomas. The first was a combination of HSV-1-TK, a protein, and Valtrex, a drug used to treat viral infections like cold sores and chickenpox.

HSV-1-TK turns Valtrex into a cytotoxic compound that kills actively dividing cancer cells. The second was Flt3L, a protein that recruits essential immune cells to the brain.

When used in combination, these therapies showed exciting early results, including improved survival, the researchers said.

Of the 18 patients enrolled in the trial, six survived more than two years, three survived more than three years, and one patient, who is still alive at the time of publication, survived up to five years, they said.

With current standard-of-care, the life expectancy for a tumour of this kind of just over 14 months.

The study found that this treatment wasn't toxic to the patients, suggesting that the highest dose used in this trial could be used in future trials.

Though the adenoviral gene therapy vectors were supposed to be active for up to a month, the researchers discovered that activity from the adenoviral vector expressing the HSV1-TK was active for up to 17 months.

This discovery changes expectations of adenoviral gene therapy in the brain and extends the potential time during which the combination HSV1-TK and Valtrex might be harnessed to combat tumour recurrence, the researchers said.

"This originated from a theoretical idea based on evolutionary hypotheses and was first tested in experimental models of the disease," said Pedro Lowenstein, a professor at U-M.

"Finally, after many years, we're thrilled to report the results of testing this approach in human patients, obtaining results that will lead to better treatments for this group of brain tumor patients," said Maria Castro, a professor at U-M.

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