Department of Biomedical Engineering, University of Virginia, Charlottesville, VA.
Department of Pathology, University of Virginia, Charlottesville, VA.
Theranostics. 2017 Aug 23;7(15):3608-3623. doi: 10.7150/thno.21225. eCollection 2017.
Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies. Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems. With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy. Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system. One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue. When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma. Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue. In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease. We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings. Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area.
免疫疗法迅速成为治疗多种转移性癌症以及许多其他病理的基础，同时，一些新的引人注目的研究揭示了中枢神经系统和免疫系统之间的显著联系。随着这些最新的发展，利用免疫系统治疗脑部疾病是一种很有前途的策略。在这里，我们认为磁共振图像引导聚焦超声（FUS）代表了一种非侵入性的方法，它将允许在中枢神经系统中进行有利的治疗性免疫调节。将有效的免疫治疗药物递送到大脑的一个障碍是血脑屏障（BBB），它是指大脑毛细血管的特殊结构，阻止大多数治疗药物从血液进入脑组织。当在循环微泡存在的情况下应用时，FUS 可以安全地和暂时地打开 BBB，以促进免疫治疗剂递送到脑实质中。此外，已经证明通过 FUS 对组织微环境的物理扰动可以调节正常和患病组织中的免疫反应。在这篇综述文章中，我们提供了 FUS 能量方案和相应的组织生物效应概述，然后回顾了关于 FUS 在正常脑和脑部疾病的临床前模型中用于治疗性抗体递送的文献。我们概述了证明 FUS 介导的在大脑和外周环境中的免疫调节的研究。最后，我们对 FUS 免疫治疗面临的挑战和在该领域进一步发展的机会发表了评论。
