Co-Clinical Research Resource for Imaging Tumor Associated Macrophages

肿瘤相关巨噬细胞成像联合临床研究资源

• 批准号: 10688045
• 负责人: Heike Elizabeth Daldrup-Link
• 金额: $ 63.91万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688045
• 关键词: Aftercare; Animal Model; Biological Markers; Blocking Antibodies; CD47 gene; Cell physiology; Cell surface; Cells; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Communities; Computer software; Consensus; Darkness; Data; Data Pooling; Development; Diagnosis; Disease; Eating; Elements; FDA approved; Goals; Growth; Healthcare; Histology; Hour; Image; Imaging Device; Imaging Techniques; Immunotherapy; Industry; Injections; Institution; Integral Membrane Protein; Intravenous; Investigation; Learning; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Methods; Monitor; Monoclonal Antibodies; Monoclonal Antibody Therapy; Multi-Institutional Clinical Trial; Necrosis; Neoplasm Metastasis; Operative Surgical Procedures; Outcome Measure; Patient-Focused Outcomes; Patients; Phagocytes; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Positioning Attribute; Prediction of Response to Therapy; Protocols documentation; Reference Standards; Reproducibility; Research; Research Personnel; Resources; SHPS-1 protein; Signal Transduction; Speed; Standardization; Testing; Therapeutic; Time; Translating; Tumor-associated macrophages; Work; anticancer activity; cancer cell; cancer clinical trial; cancer imaging; cancer immunotherapy; cancer therapy; chemotherapy; clinical application; clinical imaging; clinical investigation; clinical translation; co-clinical trial; comparative efficacy; design; efficacy study; ferumoxytol; first-in-human; imaging approach; imaging biomarker; imaging modality; imaging study; immunomodulatory therapies; improved; improved outcome; in vivo; interest; intravenous injection; iron oxide nanoparticle; iron supplement; mouse model; nanoparticle; neoplastic cell; next generation; novel; novel therapeutics; off-label use; osteosarcoma; patient population; pediatric patients; pre-clinical; preclinical imaging; preclinical study; predicting response; quantitative imaging; receptor; response; sarcoma; treatment response; treatment stratification; tumor; tumor eradication; tumor growth; tumor progression; uptake; web-accessible

Co-Clinical Research Resource for Imaging Tumor Associated Macrophages ABSTRACT The development of quantitative imaging (QI) methods for monitoring cancer therapy response has been transformative for the development of novel cancer therapeutics. QI efforts have positioned imaging as a key element in the design of clinical trials for cancer therapy response assessment. Hence, there is increased interest by the academic and industry sectors to use web accessible research resources and develop consensus approaches to validate QI methods for the next generation of clinical trials. This is particularly relevant for assessment of cancer immunotherapy, since immunotherapy does not lead to a decrease in tumor size, at least not in the immediate post-treatment phase. Therefore, we urgently need new QI tools that can monitor tumor response to novel immunotherapies. The overall goal of our project is to optimize and validate preclinical and clinical imaging techniques for in vivo quantification of tumor associated macrophages (TAM) in osteosarcomas. Recent evidence has shown that the abundant TAM response in the microenvironment of bone sarcomas can be employed to directly attack cancer cells. Blockade of the cell surface molecule CD47 expressed on sarcoma cells resulted in activation of phagocytic anti-cancer activity from TAM and efficiently eradicated tumor cells in mouse models of osteosarcoma. 26 Preclinical studies have been finalized and a multi-center phase I clinical trial is currently being planned, with expected start date in 2021. To solve the unmet clinical need for a QI tool to monitor response to new TAM- modulating therapies, our team developed a quantitative TAM imaging test, which relies on intravenous injection of the iron supplement ferumoxytol. Ferumoxytol is composed of iron oxide nanoparticles, which are phagocytosed by TAM and can be quantified with T2*-weighted MRI 45. Since ferumoxytol is FDA-approved and can be used “off label” as a TAM biomarker, it is immediately clinically available. We showed that ferumoxytol-MRI can detect TAM in osteosarcomas in mouse models 21 and patients 25. Through this project, we will (a) optimize and validate pre-clinical quantitative imaging methods for TAM imaging in an established mouse model of osteosarcoma, (b) implement the optimized methods in a co-clinical trial in patients with osteosarcoma who are undergoing immunotherapy with CD47 mAb, and finally (c) populate a web-accessible research resource with all the data, methods, and results collected from the co-clinical investigations. Developing the proposed imaging test could represent a significant breakthrough for clinicians as a new means for treatment stratification and new gold-standard imaging test for predicting treatment response of novel immunotherapies. Our QI imaging test could be utilized to compare the efficacy of different immune-modulating therapies in preclinical settings and translate the most primising candidates to the clinic. Since the development of new therapeutic drugs is expensive and take years to complete, the immediate value and heath care impact of our QI tool could be immense.

肿瘤相关巨噬细胞成像的联合临床研究资源

项目成果

Measurement of Tumor T2* Relaxation Times after Iron Oxide Nanoparticle Administration.

氧化铁纳米颗粒给药后肿瘤 T2* 弛豫时间的测量。

• DOI: 10.3791/64773
• 发表时间: 2023
• 期刊: Journal of visualized experiments : JoVE
• 作者: Ramasamy,ShakthiKumaran;Roudi,Raheleh;Morakote,Wipawee;Adams,LisaC;Pisani,LauraJ;Moseley,Michael;Daldrup-Link,HeikeE
• 通讯作者: Daldrup-Link,HeikeE