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.
Following our earlier news story Brain cancer: groundbreaking MRI-guided gene therapy, Clark Chen, chief of stereotactic and radiosurgery and vice chairman of neurosurgery at the University of California, San Diego, has spoken exclusively to Medical News Today about how the MRI-guided gene therapy works, and what this means for the future of brain cancer treatment.
How does the MRI guided gene therapy work?
Previous efforts with gene therapy for brain cancer were largely limited by the inability to deliver the drug into the brain. Under normal conditions, the brain is protected by a physiological system called the blood-brain barrier.
Unfortunately, this natural defense mechanism also prevents drugs from reaching the cancer cells in brain tumor patients. It is estimated that less than 1% of all available drugs will cross the blood brain barrier.
We by-passed the blood brain barrier by directly injecting the gene therapy into the region of the tumor.
To ensure that the adequate amount of agent is delivered to the region of the tumor, we utilized a state-of-the art MRI technology to monitor the delivery and injection processes in real time.
The MRI-guided process provides visual confirmation that adequate amount of the therapy is delivered into the tumor. Additionally, the ability to visualize the delivery catheter in real-time prevents any unintended injury to the brain.
What are the benefits and risks of using this treatment?
To understand the benefits of the therapy, we first need to review the basis of the gene therapy. The gene therapy is based on a retro-virus engineered to selectively replicate in high grade brain cancer cells.
This virus produces an enzyme that converts the FDA approved anti-fungal drug flucytosine (5-FC) into the anti-cancer drug 5-fluorouracil (5-FU).
After the injection of the virus, the patients are treated with oral formulations of 5-FC. Tumor kill is induced when 5-FC comes into contact with cells infected with virus.
Typically, when chemotherapy is given, just about every cell in the body is exposed to the potential side-effects of the drug. The direct injection approach limits the presence of the active drug in the brain tumor and not elsewhere in the body. Consequently, the approach protects the patient from many of the intended side-effects of chemotherapy.
The virus has been tested in a large number of patients and has been shown to be safe. So the risks of the treatment relates to the surgical procedure itself. The MRI technology allows the surgeon to visualize the delivery catheter in real-time. In doing so, the surgeon can prevent any unintended injury to the brain during the procedure. So, the risk of the procedure is lowered to an absolute minimum.
All of my patients undergoing this procedure were discharged from the hospital one day after surgery and resumed their normal daily activity thereafter.
How will this change the future of brain cancer treatment?
Because of the blood brain barrier, when a drug fails to prevent the tumor from growing, it is never clear whether the drug failed because it never got to the tumor or because the drug got to the tumor but has no effect on the tumor.
With the MRI-guided injection approach, we can now begin to answer this question. If the tumor grows back in the region where the virus was injected, then we need to develop better viruses.
However, if the tumor grows only in regions where the virus was not injected, then we need to develop better ways of injecting the virus in a larger area of the brain. So, the results of this trial will fundamentally dictate the appropriate next step in terms of therapeutic development.
Can you see this new method becoming widely used?
Yes. Because the method by-passes the blood brain barrier and any drug or gene therapy can be injected under MRI guidance, the approach effectively expands the spectrum of drugs that we can use to treat brain cancers by a hundred fold.
The more drugs that we have available against brain cancer, the closer we will move toward curing this disease. For this reason, I believe that this method will become more widely used.
Interview with Honor Whiteman