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.

项目概要/摘要 细胞扩增是细胞治疗的关键步骤，但由于昂贵且复杂的生物反应器要求而受到阻碍 产生足够的细胞数量以进行足够的剂量，并且需要昂贵的试剂来增强功能 提高临床成功率。为了支持在细胞治疗工作流程中使用患者细胞，需要 用于设计用于将患者细胞从最初的 iPS 克隆群体扩展为临床相关细胞的生物反应器 剂量。这些反应器还必须适用于 cGMP 工艺并且经济高效，以实现其实用性 在医疗保健系统内。总体而言，需要临床相关的细胞扩增技术 足够强大和高效，能够实现自体细胞治疗工作流程作为一种可行的治疗方法 所有人的选择。因此，我们将解决的未满足需求是提供基于生物反应器的工作流程，以实现高效 以针对患者的方式将患者细胞转化为基于 iPS 细胞的高质量治疗药物 – 受益 药物开发商、患者、临床医生和医疗保健经济。我们的细胞扩增通用方法 (OnXpansion) 使用确定的无血清培养基并依靠受控聚集来增强旁分泌 信号传导和细胞间接触、通过低剪切灌注增强营养输送以及器官型组织生态位 生成数千个相同的球状组织，可以进一步缩放以产生足够的细胞数量 以降低成本和体力劳动的方式进行细胞治疗。我们转化该技术中心的方法 围绕降低其在精准医学方面的实用性风险并提高其在预期范围内的适用性和操作性 客户工作流程。我们的生物反应器产品高效（成本、时间、劳动力）、易于使用、自动化、可靠、 稳健、生理相关且具有临床预测性。大量未满足的需求和进入职位的低门槛 与竞争对手建立有利的联系。总体而言，Link 的产品旨在实现可靠且稳健的 高效且具有高生物保真度的精准医疗工作流程，从而实现细胞的未来 通过降低成本，患者和提供者通过简化的工作流程更容易获得治疗。