INTRODUCTION Opening of the blood-brain barrier (BBB) by pulsed low intensity ultrasound has been developed during the last decade and is now recognized as a safe technique to transiently and repeatedly open the BBB. This non- or minimally invasive technique allows for a targeted and uniform dispersal of a wide range of therapeutic substances throughout the brain, including immune cells and antibodies. METHODS In this review article, we summarize pre-clinical studies that have used BBB-opening by pulsed low intensity ultrasound to enhance the delivery of immune therapeutics and effector cell populations, as well as several recent clinical studies that have been initiated. Based on this analysis, we propose immune therapeutic strategies that are most likely to benefit from this strategy. The literature review and trial data research were performed using Medline/Pubmed databases and clinical trial registry www.clinicaltrials.gov. The reference lists of all included articles were searched for additional studies. RESULTS A wide range of immune therapeutic agents, including small molecular weight drugs, antibodies or NK cells, have been safely and efficiently delivered to the brain with pulsed low intensity ultrasound in preclinical models, and both tumor control and increased survival have been demonstrated in different types of brain tumor models in rodents. Ultrasound-induced BBB disruption may also stimulate innate and cellular immune responses. CONCLUSIONS Ultrasound BBB opening has just recently entered clinical trials with encouraging results, and the association of this strategy with immune therapeutics creates a new field of brain tumor treatment.

中文翻译：

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用低强度脉冲超声打开血脑屏障，用于对 CNS 肿瘤进行免疫调节和免疫治疗。

介绍 通过脉冲低强度超声打开血脑屏障 (BBB) 已在过去十年中得到发展，现在被认为是一种安全的瞬时和重复打开 BBB 的技术。这种非侵入性或微创技术允许在整个大脑中靶向和均匀地分散各种治疗物质，包括免疫细胞和抗体。方法 在这篇综述文章中，我们总结了使用脉冲低强度超声打开 BBB 来增强免疫疗法和效应细胞群的递送的临床前研究，以及最近启动的几项临床研究。基于此分析，我们提出了最有可能从该策略中受益的免疫治疗策略。文献综述和试验数据研究是使用 Medline/Pubmed 数据库和临床试验注册中心 www.clinicaltrials.gov 进行的。搜索所有纳入文章的参考文献列表以进行其他研究。结果 在临床前模型中，包括小分子量药物、抗体或 NK 细胞在内的多种免疫治疗药物已通过脉冲低强度超声安全有效地输送到大脑，并且在不同的研究中证明了肿瘤控制和存活率的提高。啮齿动物脑肿瘤模型的类型。超声诱导的 BBB 破坏也可能刺激先天性和细胞免疫反应。结论 超声 BBB 开放刚刚进入临床试验，结果令人鼓舞，