Improving Yield of Cellular Therapeutics Using Unique Dense Magnetic Microparticles

项目摘要 细胞疗法，包括嵌合抗原受体（CAR）T细胞、自然杀伤（NK）细胞和T细胞受体 (TCR)，已经证明了治疗血液癌症的有希望的结果。制造的这些 细胞疗法开始于从血液中收集和富集足够数量的所需关键细胞， 患者或捐赠者。Raven Biomaterials计划展示速度和效率的显着提高 并且与目前用于富集所需关键细胞的细胞分离方法相比， 细胞治疗的起始材料。我们的初步数据表明，快速，有效[高产率，高纯度]， 大大改进细胞治疗起始材料的成本有效的细胞分离和富集方法 质量.我们的细胞分离方法能够改善抗体结合、颗粒分散和磁性。 利用我们的免疫磁性颗粒独特物理性质的差异进行分离，提供： 表面涂层用于粘结，比现有磁性材料密度高4倍，磁化率高20- 50倍 珠粒分离颗粒。在初步研究中，我们已经证明了> 97%的所需细胞的高回收率 同时快速[< 5分钟]消耗> 99%的小2-10 ml中的不需要的细胞[CD 4+、CD 8+和CD 15 +]， 使用简单的磁性样品体积。根据产品文献，当前竞争电池 分离产品只能回收30-70%的所需细胞，需要专门的磁性仪器， 使所需的电池暴露于可降低电池功能性的应力。在本提案中，我们旨在扩大 磁性颗粒/抗体组合的应用，以满足细胞治疗制造商的需求， 在更大的白细胞分离样本体积（单采）中优化我们的细胞分离和富集性能 袋）。该第一阶段项目的目标是持续实现选定细胞的>98%回收率 对于至少3种细胞类型，白细胞去除术样品中不需要的细胞消除>99%的群体。在 在第二阶段，我们将进一步扩大我们改进的细胞分离和富集与额外的磁性颗粒， 抗体组合的治疗细胞类型，我们将开发简单的设备，自动化细胞 富集过程。

PROJECT SUMMARY Cell therapies, including Chimeric Antigen Receptor (CAR) T cells, natural killer (NK) cells, and T cell receptor (TCR), have demonstrated promising results for treating hematological cancers. The manufacturing of these cell therapies begins by collecting and enriching an adequate number of desired critical cells from the blood of patients or donors. Raven Biomaterials plans to demonstrate a significant increase in speed and efficiency and a reduction in cost over current cell separation methodologies used to enrich the desired critical cells in cell therapy starting material . Our preliminary data has shown a rapid, efficient [high yield, high purity], and cost-effective cell separation and enrichment methodology to greatly improve cell therapy starting material quality. Our cell separation methodology enables improved antibody binding, particle dispersion and magnetic separation leveraging the differences in unique physical properties our immunomagnetic particles provides: surface coat for binding, 4x higher density and 20-50x higher magnetic susceptibility than current magnetic bead separation particles. In preliminary studies we have demonstrated high recovery > 97% of desired cells while rapidly [< 5 minutes] depleting > 99% of unwanted cells [CD4+, CD8+, and CD15+] in small 2-10 ml specimen volumes using simple magnetics. According to product literature, current competitive cell separation products only recover 30-70% of the desired cells, require specialized magnetic instruments, and expose the desired cells to stress that can lower cell functionality. In this proposal, we aim to expand the types of magnetic particle / antibody combinations to address the needs of cell therapy manufacturers, and to optimize our cell separation and enrichment performance in larger leukapheresis specimen volumes (apheresis bags). The goal of this Phase I project is to consistently achieve a >98% recovery of a selected cell population with a depletion of >99% of unwanted cells from leukapheresis samples for at least 3 cell types. In Phase II we will further expand our improved cell separation and enrichment with additional magnetic particle / antibody combinations for therapeutic cell types, and we will develop simple equipment to automate the cell enrichment process.