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）的治疗已经显示出令人难以置信的效果。 作为癌症患者的个性化免疫疗法的潜力，其涉及富集和修饰 免疫细胞表达针对癌细胞的靶向部分。研究表明，衍生疗法 具有上级效力和持续反应， 来自异源群体的疗法，代表了细胞疗法的发展方向 工业，以应对更复杂和难以捉摸的疾病。不幸的是，目前的细胞纯化 诸如流式细胞术和磁辅助细胞分选的平台努力平衡通量， 精确富集靶细胞亚群所需的定量能力， 精确的免疫疗法我们推断，一种平衡定量细胞分选能力与高 吞吐量的运作将缓解这一瓶颈，并使发展更加细致入微， 多方面的治疗通过初步研究，我们展示了一个基于技术的原型平台， 称为棘轮细胞仪，可以通过多重检测实现靶细胞亚群的定量分选 在磁珠强度上。在这个建议中，我们的目标是开发一个高通量的批量纯化柱 以及可以直接从复杂的生物基质样品中精确富集靶细胞亚群的仪器， 例如白细胞透析器或单采血液成分产品。在第一阶段，我们将重点优化定量分离 参数以最大化多种靶细胞类型的捕获和纯度。在第二阶段，我们将重点关注 平台，以满足细胞制造的吞吐量要求。

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.