EFFICIENT SCALE-UP OF IPS CELLS FOR AUTOLOGOUS CELL THERAPY WORKFLOW

高效扩大 IPS 细胞的自体细胞治疗工作流程

• 批准号: 10822298
• 负责人: Kacey Ronaldson
• 金额: $ 27.56万
• 依托单位: LINK BIOSYSTEMS INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10822298
• 关键词: Autologous; Benchmarking; Biological; Bioreactors; Cell Count; Cell Culture Techniques; Cell Death; Cell Therapy; Cells; Clinical; Complex; Cyclic GMP; Development; Devices; Dose; Engineering; Feedback; Flow Cytometry; Future; Generations; Germ Cells; Goals; Harvest; Healthcare Systems; Human; In Vitro; Karyotype determination procedure; Laboratories; Link; Maintenance; Manuals; Marketing; Measurement; Medicine; Modeling; Nutrient; Outcome; Output; Paracrine Communication; Patients; Perfusion; Pharmaceutical Preparations; Phase; Physiological; Population; Positioning Attribute; Process; Provider; Quality Control; Research; Sampling; Serum-Free Culture Media; Small Business Innovation Research Grant; Structure; Suspensions; Techniques; Technology; Time; Tissue Culture Techniques; Tissues; Training; Translating; Translations; Universities; Variant; Work; cell type; clinical predictors; clinically relevant; commercial application; cost; cost efficient; design; experimental study; health care economics; improved; in silico; induced pluripotent stem cell; innovation; manufacturing process; pluripotency; precision medicine; preservation; prototype; scale up; shear stress; stem; stem cell expansion; success; three dimensional cell culture; timeline; user-friendly

Project Summary/Abstract Cell expansion is a critical step for cell therapy, hindered by expensive and complex bioreactor requirements to yield sufficient cell numbers for adequate dosing and requiring expensive regents to enhance functionality for increased clinical success. To support the use of patient cells within the cell therapy workflow, there is a need for bioreactors designed for expanding patient cells from an initial iPS clonal population to clinically relevant cell doses. These reactors must also be suitable for cGMP processes and economically efficient to enable their utility within the healthcare system. Overall, there is a need for clinically relevant cell expansion technologies that are robust and efficient enough to enable the realization of autologous cell therapy workflows as a viable treatment option for all. Thus, the unmet need we will address is providing a bioreactor-based workflow for the efficient translation of patient cells into high-quality iPS cell based therapeutics in a patient-specific manner – benefiting drug developers, patients, clinicians, and the healthcare economy. Our universal approach to cell expansion (OnXpansion) uses a defined serum-free media and relies on controlled aggregation for enhanced paracrine signaling and cell-cell contact, enhanced nutrient delivery via low-shear perfusion, and organotypic tissue niches to generate thousands of identical spheroid tissues that can be further scaled to yield adequate cell numbers for cell therapy at both reduced costs and manual labor. Our approach to translating this technology center around de-risking its utility for precision medicine and increasing its suitability and handling within the intended customer workflows. Our bioreactor products are efficient (cost, time, labor), easy to use, automated, reliable, robust, physiologically relevant, and clinically predictive. The large unmet need and low barrier for entry positions Link favorably against competitors. Overall, Link’s products are designed to enable a reliable and robust precision medicine workflow that is efficient and of high biological fidelity, thereby enabling a future where cell therapy is more accessible to the patient, via decreased costs, and the provider, via simplified workflows.

项目摘要/摘要 细胞扩展是细胞疗法的关键步骤，受到昂贵且复杂的生物反应器要求的阻碍 产生足够的单元格数以进行足够的给药，并需要昂贵的摄政量以增强功能 增加临床成功。为了支持在细胞疗法工作流程中使用患者细胞的使用，需要 对于旨在将患者细胞从初始IPS克隆人群扩展到临床相关细胞的生物反应器 剂量。这些反应堆还必须适合CGMP过程，并且在经济上有效以实现其效用 在医疗保健系统中。总体而言，需要临床相关的细胞扩展技术 足够强大而有效的效率足以实现自体细胞疗法工作流程作为可行的治疗 所有人的选项。这就是我们要解决的未满足的需求是为有效的基于生物反应器的工作流提供 以特定于患者的方式将患者细胞转换为高质量的IPS基于IPS细胞的治疗 - 受益 药物开发人员，患者，临床医生和医疗保健经济。我们的通用细胞扩展方法 （onxpansion）使用定义的无血清培养基，并依赖于控制的聚合来增强旁分泌 信号传导和细胞 - 细胞接触，通过低剪切灌注增强的营养递送以及有机组织 为了产生数千种相同的球体组织，可以进一步缩放以产生足够的细胞数量 用于降低成本和体力劳动的细胞疗法。我们翻译该技术中心的方法 围绕其用于精确医学的实用程序，并增加其在预期的中的适用性和处理 客户工作流程。我们的生物反应器产品高效（成本，时间，人工），易于使用，自动化，可靠， 强大的，身体上的相关和临床预测性。进入位置的巨大未满足需求和低障碍 与竞争对手有利地联系。总体而言，Link的产品旨在实现可靠，强大的 精密医学工作流程效率高且具有高生物学保真度，从而使未来能够在其中 通过降低的成本和提供者，患者可以通过简化的工作流程更容易获得治疗。