Brain cancer: groundbreaking mri-guided gene therapy

Brain cancer: groundbreaking mri-guided gene therapy

Neurosurgeons from the University of California, San Diego (UCSD) have conducted the first real-time MRI-guided gene therapy for patients with brain cancer, advancing the clinical trial of new cancer drug, Toca 511.

The new treatment, carried out by neurosurgeons at the UCSD School of Medicine and the UCSD Moores Cancer Center, uses real-time magnetic resonance imaging (MRI) as a way of guiding the delivery of the new gene therapy directly into brain tumors.

MRI navigational technology, called Clearpoint, enables the neurosurgeons to inject Toca 511 (vocimagene amiretrorepvec) directly into a brain tumor.

How the MRI technology works

Clearpoint provides visual confirmation that the correct amount of Toca 511 is injected into the tumor, and it ensures physicians are able to make adjustments to optimize the location of drug delivery.

Clark Chen, chief of stereotactic and radiosurgery and vice chairman of neurosurgery at UCSD Health System, says this new method may be preferable to chemotherapy.

"With chemotherapy," Chen says. "Just about every human cell is exposed to the drug's potential side-effects. By using the direct injection approach, we believe we can limit the presence of the active drug to just the brain tumor and nowhere else in the body." he adds:

"With MRI, we can see the tumor light up in real time during drug infusion. The rest of the brain remains unaffected so the risk of the procedure is minimized."

See a fuller, exclusive interview given by Clark Chen to

How the gene therapy works

Toca 511 is a new investigational gene therapy that works as a retrovirus to selectively replicate in cancer cells, such as glioblastomas (brain tumors). Toca 511 creates an enzyme that changes an anti-fungal drug called flucytosine (5-FC), into an anti-cancer drug called 5-fluorouracil (5-FU).

Following this injection, patients are given an oral formulation of 5-FC called Toca FC. When Toca FC comes into contact with cells infected with Toca 511, the cancer cells begin to die.

Previous efforts to use gene therapy to treat brain cancer were limited, the neurosurgeons explain. The brain is usually protected by the blood-brain barrier - a natural defence mechanism. However, this barrier also prevents cancer drugs from reaching the infected cells in patients suffering from brain tumors.

But 5-FC breaks through the blood-brain barrier, meaning that direct injection of Toca 511 into the tumor enables selective chemotherapy within the tumor mass.

'Potential treatment options for several brain cancers'

The neurosurgeons say that the Clearpoint procedure is minimally invasive, and that all participants in the clinical trial were discharged from the hospital 1 day after surgery, resuming their normal routines,

Santosh Kesari, principal investigator and director of neuro-oncology at Moores Cancer Center, says this new treatment could be expanded to treat many types of brain cancer:

Inevitably, almost all glioblastoma patients fail currently available therapy. The challenge, in part, is knowing if current drugs are actually penetrating the tumor. This MRI-guided approach will help us deliver this drug into the tumor directly to see if the drug is working.

This approach may lead to new treatment options for patients battling several other types of brain cancers."

In order to be involved in this clinical trial, patients must be aged 18 or over, have a single, recurrent grade 3 or 4 giloma (a brain tumor that begins in the brain or spine), and have already had previous surgery, radiation or chemotherapy.

Phase 1 of the trial will involve investigating the stability and tolerability of Toca 511 when combined with Toca-FC (5-FC, extended-release tablets).

Brain Cancer: Leading-Edge MRI-Guided Gene Therapy (Video Medical And Professional 2020).

Section Issues On Medicine: Medical practice