High efficiency microfluidic device for large scale engineered cell therapy manufacturing

用于大规模工程细胞治疗制造的高效微流体装置

• 批准号: 10693775
• 负责人: Ryan Pawell
• 金额: $ 29.59万
• 依托单位: INDEE, INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-06 至 2024-09-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10693775
• 关键词: 3D Print; Allogenic; Autologous; Automobile Driving; Benchmarking; Blood specimen; CD3 Antigens; CD8-Positive T-Lymphocytes; Cell Separation; Cell Survival; Cell Therapy; Cell physiology; Cells; Cellular immunotherapy; Clinic; Clinical; Collaborations; Complex; Consumption; Cryopreservation; Development; Device Designs; Devices; Dose; Electroporation; Engineering; Flow Cytometry; Gene Delivery; Gene Transfer; Genes; Genetic Engineering; Goals; Human; Immune; Industry Standard; Infusion procedures; Intervention; Legal patent; Letters; Magnetic Bead Technology; Methods; Microfluidic Microchips; Microfluidics; Monoclonal Antibody HuM291; Natural Killer Cells; Optics; Outcome; Patients; Performance; Peripheral Blood Mononuclear Cell; Phase; Plant Resins; Polymers; Population; Process; Proteins; Qualifying; Recovery; Regulatory T-Lymphocyte; Research; Source; System; T-Lymphocyte; T-Lymphocyte Subsets; Technology; Testing; Time; Transfection; Veins; Viral; Whole Blood; biomaterial compatibility; chimeric antigen receptor T cells; clinical application; commercial application; cost; cost effective treatment; cytokine; cytotoxicity; design; early phase clinical trial; engineered T cells; experience; fabrication; gene therapy; improved; individual patient; instrument; magnetic beads; manufacture; manufacturing process; manufacturing technology; microfluidic technology; novel; novel therapeutics; nucleic acid delivery; preclinical study; pressure; prototype; research and development; research clinical testing; scale up; success

The goal of this project is to demonstrate the feasibility of a gentle and high-yield microfluidic device for the enrichment and capture of CD3+ T cells, for use in manufacturing autologous and allogenic engineered cell therapies. Despite impressive clinical results CAR-T and other engineered cell therapies, manufacturing these products is time consuming and costly. The ideal solution is one that could process whole blood, including target cell enrichment and genetic engineering, with minimal human intervention. Indee. Inc. previously developed Hydropore™, a microfluidic technology that has been optimized for the delivery of genes and constructs to immune cells (e.g., T-cells). Hydropore™ is a reliable and rapid alternative to current transfection approaches that yields tens to hundreds of millions of high-quality engineered cells negligible impact on cell viability and function. However, immune cells must be isolated and enriched from whole blood prior to transfection, a cumbersome, multistep process that introduces variability in the final cell product. Therefore, the Phase I objective is to develop a microfluidic device that is similarly optimized for T cell isolation and enrichment. Studies will focus on (1) the design and qualification of prototype device that is compatible with the Hydropore instrument, (2) device optimization to maximize the viability and yield of isolated cells, and (3) demonstrating the performance of the optimized T cell capture device in improving the quality and yield of engineered T cells. The success of this project will demonstrate the feasibility of a high-yield T cell enrichment device that will not only improve the source material for cellular immunotherapies but also make the manufacturing process more robust and reliable, and ultimately providing more potent and cost-effective therapies that will benefit more patients.

本项目的目标是证明一个温和的和高产量的微流控装置的可行性， 用于制备自体和同种异体工程化细胞的CD 3 + T细胞的富集和捕获 治疗尽管CAR-T和其他工程细胞疗法的临床结果令人印象深刻，但制造这些细胞仍然是一个挑战。 产品既费时又费钱。理想的解决方案是可以处理全血（包括目标）的解决方案 细胞富集和基因工程，以最少的人为干预。没错Inc.以前开发 Hydropore™是一种微流控技术，已优化用于将基因和构建体递送至 免疫细胞（例如，T细胞）。Hydropore™是目前转染方法的可靠和快速替代方法 这会产生数千万至数亿个高质量的工程细胞，对细胞活力的影响可以忽略不计， 功能然而，在转染前必须从全血中分离和富集免疫细胞， 繁琐的多步骤过程，这在最终的细胞产品中引入了可变性。因此，第一阶段 本发明的目的是开发一种微流控装置，其类似地优化用于T细胞分离和富集。研究 将重点关注（1）与Hydropore仪器兼容的原型器械的设计和鉴定， (2)装置优化，以最大化分离细胞的活力和产量，以及（3）证明性能 优化的T细胞捕获装置在提高工程化T细胞的质量和产量方面的作用。的成功 该项目将证明高产量T细胞富集装置的可行性，该装置不仅可以提高 细胞免疫疗法的源材料，而且还使制造过程更稳健和可靠， 并最终提供更有效和更具成本效益的疗法，使更多患者受益。