Gene therapy for highly aggressive brain cancer has shown promising results using cell-killing drugs and immune stimulation.

First Phase of Human Trials

This is the first phase of human trials, and researchers from the University of Michigan Department of Neurosurgery and the Rogel Cancer Center, led by Pedro Lowenstein and Maria Castro, have developed and studied adenovirus gene therapy in their lab. Given the poor prognosis in gliomas and the limited response to treatments such as chemotherapy and radiation therapy, the team decided to use Flt3L to recruit immune cells that are not normally present in the brain. These immune cells are essential to initiate a more effective immune response to cancer.

Types of Gene Therapy

The study focused on two types of gene therapy for high-grade gliomas. The first was a combination of the HSV-1-TK protein and Valtrex, a drug used to treat viral infections such as herpes and chickenpox.

And HSV-1-TK turns Valtrex into a cytotoxic compound that kills actively dividing cancer cells. The second is Flt3L, a protein that recruits important immune cells in the brain.

When used together, these treatments have shown amazing early results, including improved survival.

Of the 18 patients who took part in the study, six lived for more than two years, three lived for more than three years, and one patient, who was still alive at the time of writing, lived to five years.

Extended Life Expectancy

With current standards of care, the average life expectancy for this type of tumor is just over 14 months.

In addition, the study showed that this treatment was not toxic to patients, indicating that the highest dose used in this study could be used in future studies.

Although it was expected that adenoviral gene therapy vectors would be active for a month, the work of three researchers (Maria Luisa Varela, Mohamed Faisal Sayed and Molly West) found that the activity of an adenoviral vector expressing HSV1-TK was active for up to a month. 17 months.

This discovery changes the prospect of gene therapy for adenoviruses in the brain and extends the potential time that the combination of HSV1-TK and Valtrex could be used to fight tumor recurrence.

Positive Outlook for Brain Tumor Patients

“This emerged from a theoretical idea based on evolutionary hypotheses and was first tested in experimental disease models,” said Lowenstein, MD, professor of neurosurgery at the University of Michigan.

“Finally, after many years, we are pleased to announce the results of human testing of this approach, with results that will lead to better care for this group of patients with brain tumors,” Castro said.

The study was published in The Lancet Oncology.

Source: Medical Express