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.

该项目的目标是证明一种温和而高产的微流控装置的可行性 浓缩和捕获CD3+T细胞，用于制造自体和同种异体工程细胞 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 产品既耗时又昂贵。理想的解决方案是可以处理包括靶标在内的全血 细胞浓缩和基因工程，只需最少的人类干预。因迪。Inc.之前开发的 水孔™，一种微流控技术，已经针对交付基因和构建物进行了优化 免疫细胞(如T细胞)。水孔™是目前转染法的一种可靠和快速的替代方法 这将产生数千万到数亿高质量的工程细胞，对细胞活力的影响可以忽略不计 功能。然而，在转基因之前，必须从全血中分离和浓缩免疫细胞，a 繁琐的多步骤过程在最终细胞产品中引入了可变性。因此，第一阶段 目的是开发一种同样优化的微流控装置，用于T细胞的分离和浓缩。研究 将侧重于(1)与水孔仪兼容的原型装置的设计和鉴定， (2)设备优化，以最大限度地提高分离细胞的活性和产量，以及(3)展示性能 优化的T细胞捕获装置在提高工程T细胞的质量和产量方面的应用。的成功之处 该项目将展示一种高产量T细胞浓缩设备的可行性，它不仅将改善 细胞免疫疗法的原始材料，也使制造过程更加坚固和可靠， 最终提供更有效、更具成本效益的疗法，使更多的患者受益。