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

该合同提案的目的是完善和商业化Hydropore，这是一种低成本，高效率的方法，用于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，该技术将从早期阶段到临床研究使细胞治疗发展现代化，从而加快向有需要的患者提供治疗。在第1阶段，Hydropore技术证明了改进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的性能，以优化构建基因编辑CAR-T细胞的效率，（2）通过开发大规模Hydropore消耗性设备来扩大Hydropore的容量，具有>5 x 10^8的细胞处理能力，以及（3）验证Hydropore平台和工艺分析。将通过已建立的方法，包括流式细胞术、体外试验和体内（小鼠）疗效研究，对处理后的细胞进行严格评价。 还将建立质量控制参数。 最终交付物定义为（1）能够稳健处理>5 x 10^8 T细胞的Hydropore仪器和设备，用于大容量细胞治疗应用，以及（2）用于制造Hydropore仪器和耗材的标准操作规程。

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.