A turnkey research platform to accelerate clinical translation of targeted immune-modulation enhanced therapies

摘要 聚焦超声（FUS）是一种早期、非侵入性技术，具有巨大的治疗潜力， 肿瘤和其他疾病。FUS为现有癌症提供了替代或补充策略 治疗方法，如手术、放射、药物递送和免疫疗法（免疫肿瘤学，或 “IO”）。最近，IO特别展示了巨大的潜力，可以在以下方面产生“改变游戏规则”的影响： 然而，IO单一疗法的应答者比例仍然很低（<25%）。是 越来越清楚的是，调节肿瘤微环境的辅助治疗，如FUS， 它已被证明是一种免疫调节剂，将是至关重要的，以继续取得进展的IO。 不幸的是，尽管经验上观察到治疗结果的改善，但 FUS在很大程度上是未知的，数据仍然不清楚如何最好地利用这种高度影响力的技术。 因此，迫切需要具有强大的机制假设检验的临床前研究。然而，在这方面， 用于临床前研究的工具在标准化、易用性、可访问性和 吞吐量我们的客户发现过程已确定缺乏图像引导FUS交付的可用性 小动物的硬件是该领域的一个关键痛点。为了解决这一需求，Sonopolitan Inc.将建设 在I期成功后，通过开发交钥匙图像引导治疗平台（“TherUS”）， 与研究FUS治疗策略相关的挑战。TherUS将提供两个核心功能：治疗 将免疫调节能量递送到组织的模态，以及引导和监测这些免疫调节能量的成像模态。 3D治疗与其他解决方案不同，新TherUS将确保准确和可重复的剂量输送 无论用户的专业知识如何， 免提技术。TherUS将通过降低癌症治疗的成本来加速新型癌症治疗的临床转化。 技术壁垒限制了广泛的获取，使技术直接掌握在 癌症生物学家和免疫学家开发尖端抗癌治疗的更广阔市场 战略布局拟议的工作将分三个阶段进行。首先，我们将改进机器人龙门架， 控制超声换能器定位，以促进多模式引导、治疗和实时 监测（例如测温）。第二，我们将开发软件，以促进治疗计划， 剂量输送确认，包括与先前治疗时间点对齐的配准算法。 最后，我们将进行几项旨在验证和确认集成设备的体内研究。希洛斯 技术代表了宽场3D机器人超声，光声和 生物发光成像系统和具有实时剂量的双模式治疗（聚焦超声和激光） 交付反馈。此外，该技术可以在未来应用于许多其他应用， 包括伤口愈合，神经和基因治疗，增加了潜在的市场和科学影响。

Abstract Focused ultrasound (FUS) is an early-stage, noninvasive technology with great therapeutic potential in oncology and other diseases. FUS offers either an alternative or complementary strategy to existing cancer treatment approaches such as surgery, radiation, drug delivery, and immunotherapy (immuno-oncology, or “IO”). Most recently, IO specifically has demonstrated enormous potential to have a “game-changing” impact in our fight against cancer, however the fraction of responders to IO monotherapy remains low (<25%). It is becoming increasingly clear that adjuvant treatments that modulate the tumor microenvironment, such as FUS, which has shown to be an immunomodulator, will be critical to continue the progress made by IO. Unfortunately, despite empirically observed improvements in treatment outcomes, the mechanisms of action of FUS are largely unknown and data remain unclear how to best make use of this highly impactful technology. Therefore, preclinical research with robust mechanistic hypothesis testing is desperately needed. However, tools to enable preclinical research are greatly lacking in standardization, ease-of-use, accessibility, and throughput. Our customer discovery process has identified the lack of availability of image-guided FUS delivery hardware for small animals as a critical pain point in the field. To address this need, SonoVol Inc. will build upon Phase I success by developing a turnkey image-guided therapy platform (“TherUS”) to remove the challenges associated with studying FUS treatment strategies. TherUS will offer two core functions: treatment modalities to deliver immune-modulation energy to tissue, and imaging modalities to guide and monitor those treatments in 3D. Unlike other solutions, the new TherUS will ensure accurate and repeatable dose delivery irrespective of user expertise in a cost-effective and high-throughput manner leveraging SonoVol’s robotic, hands-free technology. TherUS will accelerate clinical translation of novel cancer therapies by lowering the technological barriers which limit widespread access, putting the technology directly in the hands of the broader market of cancer biologists and immunologists to develop cutting-edge anticancer treatment strategies. The proposed work will proceed via three stages. First, we will improve the robotic gantry that controls ultrasound transducer positioning to facilitate multi-modal guidance, treatment, and real-time monitoring (e.g. thermometry). Second, we will develop software to facilitate treatment planning and confirmation of dose delivery, including registration algorithms for alignment to previous treatment timepoints. Lastly, we will conduct several in vivo studies designed to verify and validate the integrated device. TherUS technology represents an innovative combination of a widefield 3D robotic ultrasound, photoacoustic, and bioluminescence imaging system and bi-modal therapies (focused ultrasound and laser) with real-time dose delivery feedback. Furthermore, the technology can be applied in the future to many other applications, including wound healing, neuro, and gene therapy, increasing the potential market and scientific impacts.