High Throughput & Quantitative Cell Purification for ImmunotherapyManufacture

项目摘要 基于嵌合抗原受体(CAR)或T细胞受体(TCR)的治疗显示出令人难以置信的 作为癌症患者个性化免疫疗法的潜力，涉及丰富和修改 免疫细胞表达针对癌细胞的靶向部分。研究表明，派生疗法 来自定义明确的细胞亚群的亚群具有更好的效力和持续反应 来自异种人群的疗法代表了细胞疗法的发展方向 工业，以承担更复杂和难以捉摸的疾病。不幸的是，目前的细胞净化 诸如流式细胞术和磁辅助细胞分选等平台，努力平衡吞吐量和 为可扩展的制造精确丰富目标细胞亚群所需的定量能力 精准的免疫疗法。我们认为，一种平衡定量细胞分选能力和高分选能力的工具 产能运营将缓解这一瓶颈，并使更细微的和 多方面的治疗。在初步研究的基础上，我们展示了一个基于技术的原型平台 称为棘轮细胞术，可以通过多路复用实现对目标细胞亚群的定量分选 关于磁珠强度。在这项建议中，我们的目标是开发一种高通量的间歇式净化柱 和仪器，可以直接从复杂的生物基质样本中精确地丰富目标细胞亚群， 例如白斑或分离产品。在第一阶段，我们将重点优化定量分离 参数，以最大限度地捕获和纯度多种目标细胞类型。在第二阶段，我们将专注于扩展 满足单元制造产能要求的平台。

Project Summary Therapies based on Chimeric Antigen Receptors (CAR) or T Cell Receptors (TCR) have shown incredible potential as personalized immunotherapies for cancer patients which involves enrichment and modification of immune cells to express targeting moieties against cancer cells. Studies have shown that deriving therapies from well-defined sets of cell subpopulations have superior potency and sustained reaction compared to therapies derived from heterogenous populations and represents a direction of growth for the cell therapy industry in order to take on more complex and elusive diseases. Unfortunately, current cell purification platforms, such as flow cytometry and magnetic assisted cell sorting, struggle to balance the throughput and quantitative power needed to precisely enrich the target cell subpopulations for scalable manufacture of precision immunotherapies. We reasoned that a tool that balanced quantitative cell sorting capacity with high throughput operation would alleviate this bottleneck and enable development of more nuanced and multifaceted therapies. With preliminary studies, we demonstrated a prototype platform based on a technique called ratcheting cytometry that can achieve quantitative sorting of target cell subpopulations by multiplexing on magnetic bead strength. In this proposal, we aim to develop a high throughput batch purification cartridge and instrument that can precisely enrich target cell subpopulations directly from complex biomatrix samples, such as a leukopak or apheresis product. In phase I we will focus on optimizing the quantitative separation parameters to maximize capture and purity of multiple target cell types. In phase II we will focus on scaling the platform to meet with cell manufacturing throughput requirements.