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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：
10383730
负责人：
Ahmed El Kaffas
金额：
$ 7.93万
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 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10383730
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 immune imaging improved in vivo molecular imaging multiparametric 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 ultrasound 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.

项目总结/文摘