TOPIC 397 - MICROFLUIDIC VORTEX SHEDDING: A LOW-COST, HIGH EFFICIENCY METHOD FOR GENETIC MODIFICATION TO SUPPORT CELL ENGINEERING FOR CELL-BASED IMMUNOTHERAPIES

主题 397 - 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: 10708268
• 负责人: RYAN PAWELL
• 金额: $ 199.96万
• 依托单位: INDEE, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10708268
• 关键词: Cell Therapy; Cell Volumes; Cell physiology; Cells; Cellular immunotherapy; Computer Vision Systems; Computer software; Contracts; Development; Devices; Electrodes; Genes; Genetic; Gold; Knock-in; Knock-out; Measures; Methods; Microfluidics; Microscopy; Modernization; Modification; Mus; Optics; Patients; Performance; Phase; Phenotype; Procedures; Process; Quality Control; Signal Transduction; Supporting Cell; T-Lymphocyte; Technology; Width; base; cancer immunotherapy; cellular engineering; chimeric antigen receptor T cells; cost; design; efficacy study; improved; in vitro Assay; in vivo; instrument; instrumentation; manufacturing process; meetings; prototype; scale up; therapy development

The objective of this contract proposal is to refine and commercialize Hydropore, a low cost, high efficiency method to support manufacture of cell-based cancer immunotherapies. Meeting this objective will result in a technology that will modernize cell therapy development from early stage through clincical studies, thereby expediting the delivery of treatments to patients in need. In Phase 1 the Hydropore technology demonstrated feasability in improving the manufacturing processes of CAR-T cells. In Phase II the proposal plans to (1) scale-out Hydropore performance to optimize the efficiency of constructing gene-edited CAR-T cells, (2) scale-up Hydropore capacity with the development of a large scale Hydropore consumbable device, with >5 x 10^8 cell processing capability, and (3) validate the Hydropore platform and process analytics. Processed cells will be rigorously evaluated through established approaches, including flow cytometery, in vitro assays, and in vivo (mouse) efficacy studies. Quality control parameters will also be established. The final deliverable is defined as (1) Hydropore instrumentation and devices capable of robustly processing >5 x 10^8 T cells for large volume cell therapy applications and (2) Standard Operating Procedures for manufacturing Hydropore instruments and consumables.

该合同提案的目标是完善 Hydropore 并将其商业化，这是一种低成本、高效率的方法，支持基于细胞的癌症免疫疗法的生产。实现这一目标将产生一种技术，该技术将使细胞疗法从早期阶段到临床研究的开发现代化，从而加快向有需要的患者提供治疗。在第一阶段，Hydropore 技术展示了改进 CAR-T 细胞制造工艺的可行性。在第二阶段，该提案计划 (1) 扩大 Hydropore 性能，以优化构建基因编辑 CAR-T 细胞的效率，(2) 通过开发大型 Hydropore 消耗设备来扩大 Hydropore 容量，其中 > 5 x 10^8 细胞处理能力，以及 (3) 验证 Hydropore 平台和过程分析。处理后的细胞将通过既定方法进行严格评估，包括流式细胞术、体外测定和体内（小鼠）功效研究。 还将建立质量控制参数。 最终交付物定义为 (1) Hydropore 仪器和设备，能够稳健地处理 >5 x 10^8 T 细胞，用于大容量细胞治疗应用；(2) 用于制造 Hydropore 仪器和耗材的标准操作程序。