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Acoustic assembly of patient tumor organoids for modeling cancer immunity

用于模拟癌症免疫的患者肿瘤类器官的声学组装

基本信息

批准号：
10041819
负责人：
Feng Guo
金额：
$ 7.93万
依托单位：
TRUSTEES OF INDIANA 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 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10041819
关键词：
3-Dimensional Acoustics Address Blood specimen Breast Cancer Patient Cancer Model Cancer cell line Cell Communication Cell Culture Techniques Cell Line Cells Cellular Structures Coculture Techniques Combined Modality Therapy Development Engineering Immune Immune checkpoint inhibitor Immune system Immunotherapeutic agent In Vitro Infiltration Malignant Neoplasms Methods Microfluidics Modeling Monitor Organoids Outcome Patients Reporting Research Sampling Solid Neoplasm Structure T-Lymphocyte Testing Time Tissue Sample Tumor Immunity Tumor Tissue Variant Work Xenograft procedure cancer cell cancer immunotherapy cancer therapy cell motility cellular imaging chemotherapy clinical predictors cytotoxicity exhaustion falls high throughput screening imaging approach immune checkpoint blockade improved in vivo innovation neoplastic cell novel real-time images response scaffold screening technology development three dimensional cell culture trafficking tumor tumor microenvironment tumor-immune system interactions

项目摘要

Project Summary Modeling the native dynamic interaction between tumor and immune system is crucial for developing and testing new precision immunotherapeutic strategies, as well as predicting clinical response to innovative cancer treatments, such as immune checkpoint blockade therapy. Tremendous efforts have been focused on the development of current patient-derived cancer models including 2D primary cancer cell cultures, 3D spheroid and organoid cultures, and patient-derived xenografts (PDX). However, these models fall short of reproducing patients’ native cancer-immune interaction dynamics, largely due to their low throughput, lengthy culture periods (several weeks), lack of tumor microenvironmental components (e.g. immune cells), and/or scaffolding that interferes with T cell migration and cellular interaction. Our overall objective here is to acoustically assemble novel patient organoids that represent the microenvironmental components of a patient’s tumor in order to screen immune cell infiltration and cytotoxicity dynamics in a high-throughput and time efficient manner. Our preliminary research demonstrated the acoustic assembly of about 6,000 scaffold-free homotypic tumor spheroids in one day using standard cell lines. The proposed project aims to (1) acoustically assemble a large number of heterotypic organoids using patient tumor samples; (2) monitor the dynamic T cell interaction with acoustically-engineered patient organoids trapped on a pillar array using our microfluidic high throughput, time-lapse single cell imaging approach; and (3) determine T cell tumor dynamic infiltration and cytotoxicity or exhaustion. We expect the proposed work will yield three outcomes. First, a novel acoustic organoid model will be developed to form a high number of heterotypic patient tumor organoids. Second, this platform will be employed to study T cell tumor infiltration dynamics and exhaustion in immunosuppressive microenvironments that closely mimic the patient tumor. Third, this platform will allow high-throughput and high-efficiency screening of agents (e.g. immune checkpoint inhibitors) for the development of novel cancer immunotherapy strategies to treat solid tumors.

项目总结