Ultrasound Helps Shuttle Cancer-Killing Antibodies to the Brain

Antibody therapies harness the immune system's power to fight a broad spectrum of diseases, from cancer to infectious disease. However, until now, neurologists have yet to reap the benefits of antibody-based drugs for their patients—antibodies can't cross the blood-brain barrier (BBB). This is an endothelial cell boundary between the blood circulation and the brain's extracellular space that protects against toxins and potentially-infectious pathogens.

A team of researchers at the Sunnybrook Health Sciences Centre has finally found a way of getting cancer-killing antibody drugs past the BBB to eradicate breast cancer metastases to the brain. The technology, called MR-guided focused ultrasound, or MRgFUS temporarily makes the BBB 'leaky' such that the therapy (an antibody called trastuzumab) can cross over to the brain.

Without MRgFUS, the antibody would never get into the skull as these proteins are around 100 times bigger than compounds that typically pass through the BBB.

The scientists, led by neuromodulation expert Nir Lipsman, tested their technology in a Phase I clinical trial involving Her2-positive breast cancer patients with tumors that had spread to the brain. The researchers used a special radiotracer-infused form of trastuzumab to visualize the passage of the therapy into the brain via single-photon emission computed tomography (SPECT).

Promisingly, the SPECT images showed that after permeabilizing the BBB, the antibody-drug honed in on the brain lesions. At four months post-treatment, the patients' brain tumors shrank by between 7 to 31 percent.

According to the technology innovators, MRgFUS is particularly powerful for treating multiple brain tumors as the therapy can be selectively targeted right to the bull's eye of the lesions.

"This study adds the brainstem, cranial nerve nuclei and cerebellum to the list of regions that can be safely and precisely targeted with MRgFUS, all areas in which radiation and surgery may be limited," wrote the authors in their study that was published in Science Translational Medicine.

The team is focusing ongoing work on streamlining MRgFUS procedures so that the entire treatment experience is faster and more comfortable for patients. In addition, the researchers plan to perform follow-up trials to validate their technology further.