Delivering antibody therapy to breast cancer metastases in the brain
28 October 2021
The blood-brain barrier (BBB) impedes drug delivery to the brain, limiting the effectiveness of central nervous system (CNS) therapeutics. MR-guided focused ultrasound (MRgFUS) is a noninvasive technology that has shown promise in delivering drugs across a temporarily permeable BBB, but has not been proven in humans. Now, in a first-in-world clinical trial, researchers have demonstrated that MRgFUS can be used to safely deliver antibody therapy to breast cancer that has metastasized to the brain.
In this Phase I clinical trial for Her2-positive breast cancer patients, the team captured images of the antibody therapy, trastuzumab (or Herceptin), precisely targeting tumors in the brain after using Insightec’s Exablate Neuro focused ultrasound device to temporarily and noninvasively open the BBB and enable intravenous trastuzumab to more effectively access tumor sites. The treatment was safe and increased drug delivery into MRgFUS targeted, compared to nontargeted, lesions. The findings suggest that MRgFUS is a safe and effective method to deliver treatments across the BBB and paves the way for the use of this method for other neurological conditions.
The results from the first four patients in this 10-patient trial are published in Science Translational Medicine in the paper, “MR-guided focused ultrasound enhances delivery of trastuzumab to Her2-positive brain metastases.”
“This is the first visual confirmation that focused ultrasound can improve the delivery of targeted antibody therapy across the BBB,” said Nir Lipsman, MD, PhD, director of the Harquail Centre for Neuromodulation at Sunnybrook Health Sciences Centre in Toronto. “These are preliminary, but very promising results that with continued research have implications well beyond brain cancer for other neurological conditions, including Parkinson’s disease and Alzheimer’s disease, where the blood-brain barrier poses a challenge to drug delivery.”
Metastatic breast cancer starts in the breast and can spread to the brain, bones, liver, or other organs. Current treatments for breast cancer brain metastases include open neurosurgery, radiation, and chemotherapy. However, depending on the location and number of brain metastases, options for surgery and radiation may be limited, and it can be difficult for therapies to effectively reach tumors in the brain.
“The early data in this study suggests delivery of antibody therapy directly to tumors using focused ultrasound may impact treatment efficacy, with tumors slightly decreasing in size, with varying results for patients between 7 and 31 percent during the study—on average to 21 percent,” said Rossanna Pezo, MD, PhD, medical oncologist in the Odette Cancer Centre at Sunnybrook. “The reduction in tumor size is promising but should be interpreted with caution as further research on a larger scale is needed.”
These results set the stage for the possibility of delivering a host of both established and novel therapies for numerous brain conditions that otherwise cannot gain access to the brain.
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Also published on Genengnews.com