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Secretion responsive Hydrogels for Identification of Functional single T cells (SHIFT)

用于识别功能性单 T 细胞的分泌响应水凝胶 (SHIFT)

基本信息

批准号：
10272884
负责人：
Rebecca Schulman
金额：
$ 21.51万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-16 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10272884
关键词：
Address Adopted Adoptive Cell Transfers Antigen-Presenting Cells Antigens Aspirate substance Base Sequence Benchmarking Biological Assay Blood CD3 Antigens Caliber Cell Separation Cell Survival Cell secretion Cells Clinical Clustered Regularly Interspaced Short Palindromic Repeats Communities Cytotoxic T-Lymphocytes DNA DNA Sequence Detection Development Emulsions Encapsulated Engineering Free Will Gel Generations Human Hydrogels Immune Immunotherapy In Situ Individual Interferons Intervention Investigation Label Malignant Neoplasms Measurement Measures Mediating Methods Microfluidics Patients Peptides Phenotype Population Positioning Attribute Process Protocols documentation Rapid screening Reaction Recombinants Recovery Recovery of Function Research Signal Transduction Sorting - Cell Movement Swelling T-Lymphocyte Techniques Technology Therapeutic Tumor Antigens Tumor Escape Variant antigen-specific T cells base cancer cell cancer immunotherapy cell injury cell killing clinical application cost effective cytokine engineered T cells high throughput screening immune activation improved migration multiple omics neoplastic cell optimism particle personalized immunotherapy polymerization population based preservation prevent programs response screening small molecule therapeutic development tool treatment response tumor

项目摘要

Project Summary/Abstract Adoptive cell therapy has the potential to circumvent cancer immune evasion by employing patient-derived, tumor-specific cytotoxic T-cells to attack cancer. While promising responses of advanced cases to cancer immunotherapy bolster the optimism surrounding these therapeutic strategies, interpatient variations in treatment responses demand a new method to select highly effective tumor-specific cytotoxic T-cells for better and safe immunotherapy. We propose a high-throughput, single-cell level method for identifying and recovering highly functional T cells that secrete tumor-killing signals in the presence of tumors. Our proposed technology builds on transformational advances in the generation of droplet emulsions, secretomics, and new hydrogel-based sensing techniques we recently developed. In this assay, tumor-killing T cells and cancer cells will be encapsulated in pairs in a uniformly sized, secreted factor-sensitive hydrogel droplet using a microfluidic droplet generator. The resulting isolated reaction compartments for each cell pair will prevent the mixing of T cells' multiple secreted factors and will concentrate them to allow sensitive detection. The hydrogel will respond to a factor secreted by functional T cells via a dramatic size change, allowing hydrogels with active T cells to be reliably isolated from the heterogeneous mixture using a hydrodynamic size-based particle sorting mechanism. The sorted pairs will be individually recovered using an aspiration pipette and the hydrogel shell dissolved without cell damage, allowing for the recovery of functional individual T cells. We propose to use this high-throughput assay, capable of screening millions of T cells, to identify tumor-responsive T cells and to recover them for downstream analysis or proliferation. This assay is simple, sensitive, and versatile enough to be used by a wide research community or eventually within clinical settings for isolating and profiling rare cells with target secretory phenotypes.

项目总结/文摘