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

基本信息

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
项目类别：
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

项目摘要

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.

该项目的目标是展示一种温和且高产量的微流体装置的可行性 CD3+ T 细胞的富集和捕获，用于制造自体和同种异体工程细胞尽管 CAR-T 和其他工程细胞疗法的临床效果令人印象深刻，但仍在制造这些疗法。产品既耗时又昂贵，理想的解决方案是能够处理全血（包括目标血液）的解决方案。 Indee 公司之前开发了细胞富集和基因工程，只需极少的人为干预。 Hydropore™ 是一种微流体技术，已针对基因和构建体的递送进行了优化免疫细胞（例如 T 细胞）是当前转染方法的可靠且快速的替代方案。产生数千万到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然而，在转染之前，必须从全血中分离和富集免疫细胞。繁琐的多步骤过程会导致最终细胞产品的变异性，因此，第一阶段。目标是开发一种针对 T 细胞分离和富集研究进行类似优化的微流体装置。将重点关注 (1) 与 Hydropore 仪器兼容的原型设备的设计和鉴定， (2) 设备优化，以最大限度地提高分离细胞的活力和产量，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作用。该项目将展示高产 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原材料，同时也使制造过程更加稳健和可靠，最终提供更有效、更具成本效益的疗法，使更多患者受益。