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是存在的，但生产还有待优化，以增加这些拯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旋脱落（μVS）的持续发展来满足这一需求，μ VS是一种安全快速的基因修饰患者源性免疫细胞的方法。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工作流程中。该合同提案的目的是证明μVS技术在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）细胞方面的可行性。研究和开发目标是：（1）证明μVS转染具有临床相关CAR和TCR构建体的原代T细胞的技术性能，以及（2）证明μVS在基于细胞的试验中产生的转染T细胞的功能性和安全性。在成功完成这些目标之前，CAR-T和TCR-T细胞将使用患者来源的T细胞进行工程化，并将证明商业规模的处理和富集足够的遗传修饰活细胞用于临床应用。