Scientists have discovered a new method in the treatment of brain tumors. This is a special gene therapy in which it works to strengthen immunity. Given the poor prognosis of gliomas and limited response to treatments such as chemotherapy and radiation, the team considered using adenoviral gene therapy. The study, published in the journal ‘The Lancet Oncology’, shows that the therapy not only proved to be safe but also improved survival. Oren Sagher, professor of neurosurgery at the University of Michigan, said, "It is exciting to be able to move a novel therapy from bench to bedside in such a streamlined manner. and represents a tour-de-force in translational medicine.
First HSV-1-Vaccine
In the Phase 1 trial, the team focused on two types of genetic therapies in high-grade gliomas. The first was a combination of the HSV-1-vaccine — a protein — and Valtrex — a drug used to treat conditions such as the common cold and chickenpox. Used to treat viral infections. The HSV-1 vaccine 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 treatments showed exciting preliminary results, including improved survival. Of the 18 patients enrolled in the trial, six survived more than two years, three lived more than three years, and one patient, who was still alive at the time of publication, lived five years.
adenoviral gene therapy
However, the adenoviral gene therapy vectors were supposed to remain active for one month. The team found that the activity of the adenoviral vector expressing the HSV1-vaccine was active for up to 17 months. This finding changes expectations for adenoviral gene therapy in the brain and potentially prolongs the time during which to deal with tumor recurrence. A combination of HSV1-TK and Valtrex can be used.
“It originated from a theoretical idea based on evolutionary hypotheses and was the first time it was tested in an experimental model of disease,” said Pedro Lowenstein, professor of neurosurgery at U-M. Maria Castro, professor of neurosurgery at U-M Finally, after many years, we are thrilled to report the results of testing this approach in human patients, which will lead to better treatments for this group of brain tumor patients.
Although more work is needed before this can be brought into the clinic, the importance of long-term expression of HSV1-TK suggests implementation to improve treatment. The results of this study support the design of future Phase 1b/2 clinical trials.
