Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
J Neurooncol. 2021 Jan;151(1):65-73. doi: 10.1007/s11060-020-03425-8. Epub 2020 Feb 28.
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.
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.
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.
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.
在过去的十年中，脉冲低强度超声打开血脑屏障（BBB）的技术得到了发展，现在被认为是一种安全的技术，可以短暂且反复地打开 BBB。这种非侵入性或微创技术允许将各种治疗物质（包括免疫细胞和抗体）靶向且均匀地分散到整个大脑中。
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 以增强免疫治疗剂和效应细胞群体传递的临床前研究，以及最近已经开始的几项临床研究。基于此分析，我们提出了最有可能受益于该策略的免疫治疗策略。文献综述和试验数据研究使用了 Medline/Pubmed 数据库和临床试验注册网站 www.clinicaltrials.gov 进行。所有纳入文章的参考文献列表都被搜索了其他研究。
在临床前模型中，各种免疫治疗剂，包括小分子药物、抗体或 NK 细胞，都已通过脉冲低强度超声安全且有效地递送到大脑中，在不同类型的啮齿动物脑肿瘤模型中均证明了肿瘤控制和生存率提高。超声诱导的 BBB 破坏也可能刺激先天和细胞免疫反应。
超声 BBB 开放最近刚刚进入临床试验，并取得了令人鼓舞的结果，该策略与免疫治疗的结合为脑肿瘤治疗创造了一个新领域。
