期刊
SCIENCE ADVANCES
卷 7, 期 6, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd0772
关键词
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资金
- Ministry of Science and Technology, Taiwan [105-2221-E-182-022, 106-2221-E-182-002]
- Chang Gung Memorial Hospital, Linkou [CIRPD2E0051-53, CMRPD2D0111-13]
- National Health Research Institute [NHRI-EX109-10502NI]
- Clinical Trial Center, Chang Gung Memorial Hospital, Linkou, Taiwan - (Ministry of Health and Welfare of Taiwan) [MOHW107-TDU-B-212-123005, MOHW108-TDU-B-212-133005, MOHW109TDU-B-212-114005]
- NaviFUS Inc.
Focused ultrasound (FUS) with microbubbles can transiently open the blood-brain barrier (BBB) to increase therapeutic agent penetration, benefiting recurrent glioblastoma (rGBM) treatment. A pilot trial using a neuronavigation combined with a manually operated frameless FUS system for rGBM patients established safety and feasibility, with dose-dependent BBB-opening effect observed. Additionally, FUS-induced immune modulation was demonstrated to convert the immunosuppressive tumor microenvironment into an immunostimulatory one at a higher but safe dosage.
Focused ultrasound (FUS) in the presence of microbubbles can transiently open the blood-brain barrier (BBB) to increase therapeutic agent penetration at the targeted brain site to benefit recurrent glioblastoma (rGBM) treatment. This study is a dose-escalating pilot trial using a device combining neuronavigation and a manually operated frameless FUS system to treat rGBM patients. The safety and feasibility were established, while a dose-dependent BBB-opening effect was observed, which reverted to baseline within 24 hours after treatment. No immunological response was observed clinically under the applied FUS level in humans; however, selecting a higher level in animals resulted in prolonged immunostimulation, as confirmed preclinically by the recruitment of lymphocytes into the tumor microenvironment (TME) in a rat glioma model. Our findings provide preliminary evidence of FUS-induced immune modulation as an additional therapeutic benefit by converting the immunosuppressive TME into an immunostimulatory TME via a higher but safe FUS dosage.
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