Enabling High Yield Engineered T Cell Production by Quantitative Separation using Parallel Magnetic Ratcheting

项目摘要：通过使用定量分离实现高产量的工程T细胞生产 平行磁棘轮 个人化癌症治疗是抗癌研究的一个日益增长的领域。一件有希望的事 一种方法是使用工程T细胞来触发人体的免疫系统直接攻击 癌症。最近对嵌合抗原受体(CAR)T细胞的研究表明，它在治疗B细胞方面有效 恶性肿瘤和其他几种癌症。然而，CAR-T细胞生产面临着内在的挑战 由于转导的异质性，导致工程T细胞的性能差异很大。研究 提示CAR-T细胞疗法可以通过只分离治疗效果最佳的细胞来改进。 不幸的是，传统的细胞分离和分析方法，包括磁辅助细胞分离 (MACS)和荧光辅助细胞分离(FACS)在CAR-T的制造中具有固有的局限性 细胞疗法。MACS技术本质上是布尔的，不能用来丰富基于 在曲面标记的表达式上。或者，FACS技术是高度定量的，但不能 实际规模，以满足可接受的制造产能。Ferrologix旨在解决这些限制 在目前的CAR-T生产方法中，通过开发一种基于磁力的商用产品 微操作技术，被称为磁棘轮，由PI在加州大学洛杉矶分校开发。这是一项创新 技术将FACS的定量分析和分离能力赋予磁性细胞分离， 使得能够基于结合到其表面的颗粒数量来分离磁性标记的细胞。 Ferrologix的目标是将这种定量磁分离技术应用到细胞分离仪器中 具有能够在工业上定量浓缩治疗最佳CAR-T细胞的一次性墨盒 扩展吞吐量。如果收到，第一阶段的资金将用于开发一个原型系统，以量化 基于表面表达以105细胞/S吞吐量分离CAR-T细胞，并将用作验证 细胞制造技术，以提高新兴细胞免疫疗法的有效性。

Project Summary: Enabling High Yield Engineered T Cell Production by Quantitative Separation using Parallel Magnetic Ratcheting Personalized cancer treatments are a growing area of research in the fight against cancer. One promising approach has been the use of engineered T cells to trigger the body’s immune system to directly attack the cancer. Recent research into chimeric antigen receptor (CAR) T cells has shown efficacy in treating B-cell malignancy and several other types of cancers. However, CAR-T cell production faces inherent challenges with transduction heterogeneity, leading to large variations in performance of engineered T cells. Research suggests that CAR-T cell therapies can be improved by separating only therapeutically optimal cells. Unfortunately, traditional methods of cell separation and analysis, including magnetic assisted cell separation (MACS) and fluorescence assisted cell separation (FACS), have inherent limitations in manufacture of CAR-T cell therapies. MACS techniques are Boolean in nature and cannot be used to enrich sub-populations based on expression of a surface marker. Alternatively, FACS techniques are highly quantitative, but cannot be practically scaled to meet an acceptable manufacturing throughput. Ferrologix aims to address the limitations in current CAR-T production methods by developing a commercial product based on a magnetic micromanipulation technique, known as magnetic ratcheting, developed at UCLA by the PI. This innovative technology imparts FACS’ quantitative analysis and separation capabilities to magnetic cell separation, enabling magnetically labeled cells to be separated based on the number of particles bound to their surface. Ferrologix aims to implement this quantitative magnetic separation technology into a cell separation instrument with disposable cartridges capable of quantitatively enriching therapeutically optimal CAR-T cells at industrial scale throughputs. If received, the phase I funds will be used to develop a prototype system to quantitatively separate CAR-T cells at a 105 cell/s throughput based on surface expression and will serve as validation for a cell manufacturing technology to improve the effectiveness of emerging cellular immunotherapies.