Development of Molecular Microbubble Probes and Ultrasound-Guidance in Immunotherapeutic Strategies

免疫治疗策略中分子微泡探针和超声引导的发展

基本信息

批准号：
10057655
负责人：
Ahmed El Kaffas
金额：
$ 31.58万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10057655
关键词：
3-Dimensional Abdomen Address Adopted Adverse effects Adverse event Angiogenesis Inhibitors Binding Biological Markers Blood Vessels Cell Surface Receptors Cell surface Cells Clinic Clinical Clinical Trials Colorectal Combined Modality Therapy Complement Complex Contrast Media Development Dose Endothelial Cells Endothelium Engineering Evaluation Event FDA approved Feedback Goals Hepatic Mass Image Immune Immune checkpoint inhibitor Immune system Immunity Immunohistochemistry Immunologic Markers Immunosuppression Immunotherapeutic agent Immunotherapy Implant In Vitro Infiltration Kinetics Life Liver Malignant Neoplasms Malignant neoplasm of liver Measurement Metastatic Neoplasm to the Liver Microbubbles Molecular Mus National Institute of Biomedical Imaging and Bioengineering Nature Neoplasms in Vascular Tissue Outcome Patients Perfusion Phenotype Property Receptor Cell Research Rodent Sampling Errors Specificity Surface Therapeutic Tissue imaging Tissues Toxic effect Translations Treatment Protocols Ultrasonography Variant Vascular Endothelial Cell Vascular Endothelium anergy anticancer activity base cancer imaging cellular imaging cost design effector T cell histological studies image guided imaging approach imaging modality imaging probe immune activation immune checkpoint improved in vivo molecular imaging non-invasive imaging patient response predicting response predictive marker programmed cell death ligand 1 programs quantitative ultrasound response serial imaging success targeted agent tool treatment effect treatment response tumor tumor growth vascular abnormality

项目摘要

PROJECT SUMMARY/ABSTRACT Despite the unprecedented effects of immunotherapy in treating cancer, over 50–80% of patients will not respond to treatment and will endure severe adverse and life-threatening events due to treatment. Approaches to select or guide immunotherapeutic strategies are urgently needed. We propose to develop ultrasound-based approaches to characterize an overlooked attribute of tissue immuno-imaging; the vasculature and associated endothelium. In cancer, tumor blood vessels and associated endothelial cells are highly abnormal and immunosuppressive. These also differ extensively on a patient-by-patient basis. Approaches to modulate vascular and endothelial immunity have been developed, where anti-angiogenic agents are used to directly target these and enhance the effects of immunotherapy. However, timing and dosing of anti-angiogenics with immunotherapy remains a major challenge to maximize benefits to all patients. As such, the tools we propose to develop will help 1) select patients that are most likely to respond to immunotherapy and reduce adverse effects and costs to non-responders, and 2) provide imaging feedback for guiding combined anti-angiogenic and immunotherapy treatment regimens so that more patients may benefit from the unparalleled effects of these treatments. In order to achieve our goals, we will: 1) develop unique molecular ultrasound probes for imaging endothelial cell immunosuppressive surface markers, and 2) develop image-guidance to optimize immunotherapeutic strategies by exploring the quantitative ultrasound parameter space. Equipped with these initial developments, our goal will be to initiate a larger research program designed to further develop quantitative ultrasound approaches for imaging tissue, vascular and endothelial aspects of the immune system.

项目概要/摘要尽管免疫疗法在治疗癌症方面取得了前所未有的效果，但超过 50-80% 的患者不会对治疗有反应，并会因治疗方法而承受严重的不良和危及生命的事件。我们迫切需要选择或指导免疫治疗策略。表征组织免疫成像的惊人属性的方法；在癌症中，肿瘤血管和相关内皮细胞高度异常且异常。这些也主要根据患者的情况而有所不同。血管和内皮免疫已经发展起来，其中抗血管生成剂被用来直接靶向这些并增强免疫治疗的效果然而，抗血管生成药物的时机和剂量。免疫疗法仍然是为所有患者带来最大利益的重大挑战，因此，我们提出的工具。开发将有助于 1) 选择最有可能对免疫疗法产生反应的患者并减少不良反应对无反应者的影响和成本，2) 提供影像反馈以指导联合抗血管生成治疗和免疫疗法的治疗方案，让更多的患者受益于免疫疗法无与伦比的效果为了实现我们的目标，我们将：1）开发独特的分子超声探头。对内皮细胞免疫抑制表面标记进行成像，2) 开发图像引导以优化通过探索配备这些的定量超声参数空间来制定免疫治疗策略。初步发展，我们的目标将是启动一个更大的研究计划，旨在进一步开发用于对免疫系统的组织、血管和内皮方面进行定量成像的超声方法。