Improving Yield of Cellular Therapeutics Using Unique Dense Magnetic Microparticles

使用独特的致密磁性微粒提高细胞治疗的产量

基本信息

批准号：
10484573
负责人：
Thomas Russell
金额：
$ 40万
依托单位：
RAVEN BIOMATERIALS LLC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-09 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10484573
关键词：
Address Antibodies B-Lymphocytes Basophils Binding Biocompatible Materials Blood Blood Component Removal Blood Platelets Businesses CAR T cell therapy CD14 gene CD19 gene CD34 gene CD36 gene CD8B1 gene Cancer Patient Cell Count Cell Separation Cell Therapy Cell physiology Cells Complex Consumption Cytotoxic T-Lymphocytes Data Development Dose Equipment Erythrocytes FCGR3B gene FDA approved Goals Hematologic Neoplasms IL2RA gene IL3RA gene In complete remission Industry Legal patent Leukapheresis Leukocytes Literature Magnetism Malignant Neoplasms Manuals Manufacturer Name Methodology Molecular Monoclonal Antibodies NCAM1 gene Natural Killer Cells Patients Performance Phase Population Positioning Attribute Predisposition Probability Process Production Property Protocols documentation Raven Recovery Regulatory T-Lymphocyte Reporting Residual state Sampling Small Business Innovation Research Grant Solid Specimen Speed Stress Surface T-Cell Receptor T-Lymphocyte Techniques Technology Therapeutic Therapeutic Uses Time Work cancer immunotherapy cell type chimeric antigen receptor chimeric antigen receptor T cells commercialization cost cost effective density experience head-to-head comparison improved individualized medicine innovation instrument instrumentation interest magnetic beads manufacturing process monocyte neutrophil particle physical property prevent stem cells superparamagnetic beads

项目摘要

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.

项目摘要细胞疗法，包括嵌合抗原受体（CAR）T细胞，天然杀伤（NK）细胞和T细胞受体（TCR），已经证明了治疗血液癌的有希望的结果。这些制造细胞疗法首先收集和丰富了足够数量的来自的临界细胞病人或捐助者。乌鸦生物材料计划展示速度和效率的显着提高与当前细胞分离方法的成本降低，用于丰富所需的关键细胞细胞疗法起源物质。我们的初步数据显示出快速，有效的[高收率，高纯度]，并且具有成本效益的细胞分离和富集方法，以极大地改善细胞疗法的起始材料质量。我们的细胞分离方法可以改善抗体结合，颗粒分散和磁性利用我们免疫磁颗粒的独特物理特性差异的分离提供：表面涂层的结合，密度高4倍，磁化率高20-50x 珠分离颗粒。在初步研究中，我们证明了高恢复> 97％的所需细胞在小2-10 mL中，迅速[<5分钟]耗尽> 99％的不需要细胞[CD4+，CD8+和CD15+] 使用简单磁化的标本体积。根据产品文献，当前的竞争细胞分离产品仅恢复30-70％的所需单元，需要专用的磁性仪器，并且将所需的细胞暴露于可以降低细胞功能的压力。在此提案中，我们旨在扩展类型磁性颗粒 /抗体组合，以满足细胞治疗制造商的需求，并优化我们的细胞分离和富集性能，以较大的白细胞发音标本体积包）。该阶段I项目的目标是始终达到所选单元的> 98％的回收率至少3种细胞类型的白细胞膜样品中耗尽> 99％的不良细胞的耗竭。在第二阶段，我们将进一步扩大我们改善的细胞分离和富集，并使用其他磁性颗粒 / 治疗细胞类型的抗体组合，我们将开发简单的设备以使细胞自动化丰富过程。