World-first Clinical Trial Demonstrates Focused Ultrasound Can Deliver Antibody Therapy to Breast Cancer Metastases in the Brain

October 14, 2021 — In a first-in-world clinical trial, researchers atSunnybrook Health Sciences Centrein Toronto, Canada, have demonstrated that magnetic resonance (MR)-guided focused ultrasound can be used to safely deliver antibody therapy tobreast cancerthat has metastasized to the brain.

In this Phase I clinical trial for Her2-positive breast cancer patients, the Sunnybrook team captured images of the antibody therapy, trastuzumab (or Herceptin), precisely targeting tumors in the brain after using Insightec’sExablate Neuro聚焦超声设备暂时和无创地打开血脑屏障(BBB)，并使静脉曲妥珠单抗更有效地进入肿瘤部位。

抗体疗法可以帮助免疫系统对抗癌细胞，通常与放疗和化疗结合使用。然而，当血脑屏障试图瞄准大脑中的位置时，它提出了一个挑战。血脑屏障是血管内壁的一层细胞，保护大脑免受病毒、细菌和其他毒素的伤害，但它也可以阻止治疗药物，如曲妥珠单抗，以足够高的浓度到达大脑，从而发挥作用。

“This is the first visual confirmation that focused ultrasound can improve the delivery of targeted antibody therapy across the BBB,” said Nir Lipsman, M.D., thestudy’sprincipal investigator and director of the Harquail Centre for Neuromodulation at Sunnybrook. “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, where the blood-brain barrier poses a challenge to drug delivery.”

The results from the first four patients in this 10-patient trial were published today inScience Translational Medicinein an article titled “MR-guided focused ultrasound enhances delivery of Trastuzumab to Her2-positive brain metastases.”

Metastatic breast cancer, also known as Stage IV breast cancer, startsin 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, M.D., 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.

Sunnybrook is a Focused Ultrasound Center of Excellence – the only Canadian site to be recognized as such by the Focused Ultrasound Foundation, which was one of the funders of this clinical trial.

“Sunnybrook的多学科团队是使用聚焦超声治疗各种脑部疾病的先驱，”基金会主席Neal F. Kassell医学博士说。“这项世界上首次的研究证明了聚焦超声打开血脑屏障的有效性，从而促进抗体输送到大脑，这是开发治疗脑肿瘤和其他神经疾病新方法的一个重要里程碑。我们很高兴能与这个受人尊敬的集团合作。”

For more information:www.fusfoundation.org