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

加速靶向免疫调节增强疗法临床转化的交钥匙研究平台

• 批准号: 10458077
• 负责人: Tomasz Joseph Czernuszewicz
• 金额: $ 76.21万
• 依托单位: SONOVOL, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-11 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10458077
• 关键词: 3-Dimensional; Acceleration; Acoustics; Address; Adjuvant; Algorithms; Animal Model; Animals; Articulation; Basic Science; Breast Cancer Model; Clinic; Clinical; Collaborations; Communities; Complex; Computer software; Custom; Data; Detection; Development; Devices; Disease; Dose; Drug Delivery Systems; Engineering; Ensure; Equipment; Feedback; Focused Ultrasound; Focused Ultrasound Therapy; Foundations; Future; Geometry; Hand; Image; Immune Targeting; Immunologist; Immunology; Immunomodulators; Immunooncology; Immunotherapy; Industry; Institution; Interview; Intuition; Lasers; Letters; Low-Level Laser Therapy; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Modality; Monitor; Neurology; Oncology; Operative Surgical Procedures; Optics; Pain; Patients; Performance; Pharmaceutical Preparations; Phase; Physicians; Positioning Attribute; Process; Publishing; Radiation; Radiation therapy; Reproducibility; Research; Research Design; Research Personnel; Robotics; Rodent Model; Running; Scientist; Site; Standardization; Surgical incisions; Surveys; System; Techniques; Technology; Testing; Therapeutic; Thermometry; Three-Dimensional Image; Time; Tissue imaging; Tissues; Training; Transducers; Translations; Treatment outcome; Ultrasonic Transducer; Ultrasonography; United States National Institutes of Health; Validation; Work; anticancer research; anticancer treatment; base; bioluminescence imaging; cancer therapy; clinical application; clinical translation; clinically translatable; commercialization; cost effective; effective therapy; experimental study; fight against; flexibility; gene therapy; image guided; image guided therapy; imaging modality; imaging system; immunoregulation; improved; in vivo; innovation; instrument; multimodality; new technology; novel; open source; pancreatic cancer model; photoacoustic imaging; pre-clinical; pre-clinical research; preclinical study; prototype; real time monitoring; research and development; software development; subcutaneous; success; tool; treatment planning; treatment response; treatment strategy; tumor microenvironment; ultrasound; user-friendly; validation studies; wound healing

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.

抽象的 专注超声（FUS）是一种早期的无创技术，具有巨大的治疗潜力 肿瘤学和其他疾病。 FUS为现有癌症提供了替代或完整的策略 治疗方法，例如手术，放射，药物输送和免疫疗法（免疫肿瘤学或 “ io”）。最近，IO专门表现出具有“改变游戏规则”影响的巨大潜力 我们与癌症的斗争，但是IO单一疗法的响应者的一部分仍然很低（<25％）。这是 越来越清楚地，调整调节肿瘤微环境（例如FUS）的处理 已经证明是一种免疫调节剂，对于继续IO取得的进度至关重要。 不幸的是，dospit迫切观察到治疗结果的改善，作用机理 FUS在很大程度上是未知的，并且数据尚不清楚如何最好地利用这项高度影响力的技术。 因此，迫切需要使用强大的机械假设检验进行临床前研究。然而， 实现临床前研究的工具极少缺乏标准化，易用性，可访问性和 吞吐量。我们的客户发现过程已经确定缺乏图像引导的FUS交付的可用性 小动物的硬件是该领域的关键疼痛点。为了满足这一需求，Sonovol Inc.将建立 在第一阶段成功时，通过开发交钥匙图像引导的治疗平台（“ therus”）来删除 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 向组织传递免疫调节能量的方式，并成像指导和监视这些方式 3d的治疗。与其他解决方案不同，新的Therus将确保准确且可重复的剂量递送 无论用户专业知识如何以具有成本效益且高通量的方式利用Sonovol的机器人， 免提技术。 Therus将通过降低新型癌症疗法的临床翻译来加速 限制宽度访问的技术障碍，将技术直接掌握在 癌症生物学家和免疫学家的更广泛市场，以开发尖端的抗癌治疗 策略。拟议的工作将通过三个阶段进行。首先，我们将改善机器人龙门 控制超声传感器定位，以促进多模式指导，治疗和实时 监测（例如温度法）。其次，我们将开发软件以促进治疗计划和 确认剂量递送，包括与以前的治疗时间点对齐的注册算法。 最后，我们将进行几项旨在验证和验证集成装置的体内研究。 Therus 技术代表了广场3D机器人超声，光声和 具有实时剂量的生物发光成像系统和双模式疗法（聚焦超声和激光） 送货反馈。此外，该技术将来可以应用于许多其他应用程序， 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。