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: 10325591
• 负责人: Tomasz Joseph Czernuszewicz
• 金额: $ 123.74万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325591
• 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; response; software development; subcutaneous; success; tool; treatment planning; treatment strategy; tumor microenvironment; 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.

摘要 聚焦超声(FUS)是一种早期的、无创的技术，具有巨大的治疗潜力。 肿瘤学和其他疾病。FUS为现有癌症提供了一种替代或补充策略 治疗方法，如手术、放射、药物输送和免疫治疗(免疫肿瘤学、或 “IO”)。最近，IO在以下方面显示出了巨大的潜力，可以带来改变游戏规则的影响 我们与癌症的斗争，然而，IO单一疗法的应答者比例仍然很低(&lt；25%)。它是 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，将是继续IO取得的进展的关键。 不幸的是，尽管从经验上观察到治疗结果有所改善，但卡介苗的作用机制 FU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项高度有影响力的技术。 因此，迫切需要具有稳健的机械性假设检验的临床前研究。然而， 支持临床前研究的工具在标准化、易用性、可获得性和 吞吐量。我们的客户发现流程已确定缺少图像引导的FUS交付 小动物的硬件是该领域的一个关键痛点。为了满足这一需求，SonoVol Inc.将建立 在第一阶段成功后，通过开发交钥匙图像引导治疗平台(“TherUS”)来移除 与研究FUS治疗策略相关的挑战。Therus将提供两项核心功能：治疗 向组织传递免疫调节能量的方式，以及引导和监测这些功能的成像方式 3D模式下的治疗。与其他解决方案不同，新的TherUS将确保准确和可重复的剂量传递 无论用户以经济高效和高吞吐量的方式利用SonoVol的机器人， 免提技术。TherUS将通过降低 限制广泛使用的技术壁垒，将技术直接掌握在 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。拟议的工作将分三个阶段进行。首先，我们将改进机器人门架 控制超声换能器定位，以促进多模式指导、治疗和实时 监测(如测温)。第二，我们将开发软件，促进治疗规划和 剂量传递的确认，包括与以前的治疗时间点对齐的登记算法。 最后，我们将进行几项活体研究，旨在验证和验证集成设备。塞鲁斯 这项技术代表了广泛领域的3D机器人超声、光声和 生物发光成像系统和实时剂量的双模治疗(聚焦超声和激光) 送货反馈。此外，该技术在未来还可以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。