Microfluidic vortex shedding: a low-cost, high efficiency method for genetic modification to support cell engineering for cell-based immunotherapies

微流控涡流脱落：一种低成本、高效的基因修饰方法，支持基于细胞的免疫疗法的细胞工程

• 批准号: 10260803
• 负责人: JUSTIN JARRELL
• 金额: $ 39.93万
• 依托单位: INDEE, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-08 至 2021-06-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260803
• 关键词: Adult; Biological Assay; CD3 Antigens; CTAG1 gene; Cell Survival; Cells; Cellular immunotherapy; Contracts; DNA; Development; Electroporation; Engineering; Gene-Modified; Genetic; Goals; Human; Immune; Immunotherapy; Life; Methods; Microfluidics; Modification; Patients; Performance; Recovery; Safety; Savings; Supporting Cell; T-Cell Receptor; T-Lymphocyte; Technology; Transfection; Transposase; Viral; base; cancer immunotherapy; cellular engineering; chimeric antigen receptor T cells; clinical application; clinically relevant; cost; meetings; open source; research and development

Personalized gene-modified cell immunotherapies exist, but manufacturing has yet to be optimized to increase the broad availability of these life-saving therapies to patients in need. This proposal is focused on meeting this need with the continued development of microfluidic vortex shedding (μVS), a safe and rapid approach to genetically modify patient-derived immune cells. The long term objective of this proposal is to integrate μVS into the manufacturing workflow of cell-based cancer immunotherapies. The goal of this contract proposal to demonstrate the feasibility of μVS technology in generating representative Chimeric Antigen Receptor T cells (CAR-T) and T Cell Receptor T cells (TCR-T) cells. The research and development objectives are to: (1) demonstrate the technical performance of μVS transfection of primary T cells with clinically relevant CAR and TCR constructs, and (2) demonstrate the functionality and safety of transfected T cells generated by μVS in cell based assays. Pending the successful completion of these objectives, CAR-T and TCR-T cells will be engineered using patient-derived T cells, and commercial-scale processing and enrichment of sufficient genetically modified viable cells for clinical applications will be demonstrated.

个性化的基因修饰细胞免疫疗法已经存在，但制造仍有待优化，以提高这些挽救生命的疗法对有需要的患者的广泛可用性。该提案的重点是通过微流体涡流脱落（μVS）的持续发展来满足这一需求。 ，一种安全、快速的方法来对患者来源的免疫细胞进行基因改造。该提案的长期目标是将 μVS 整合到基于细胞的癌症免疫疗法的制造流程中。该合同提案的目标是证明 μVS 的可行性。产生代表性嵌合抗原受体T细胞（CAR-T）和T细胞受体T细胞（TCR-T）细胞的技术研发目标是：（1）展示μVS转染原代T细胞的技术性能。临床相关的 CAR 和 TCR 构建体，以及 (2) 在基于细胞的测定中证明 μVS 生成的转染 T 细胞的功能和安全性，在成功完成这些目标之前，CAR-T 和 TCR-T 细胞将被开发。将展示使用患者来源的 T 细胞进行工程改造，以及用于临床应用的足够的转基因活细胞的商业规模加工和富集。