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

基本信息

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
项目类别：
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

项目摘要

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为了支持在细胞治疗工作流程中使用患者细胞，需要提高临床成功率。用于设计用于将患者细胞从初始 iPS 克隆群扩展为临床相关细胞的生物反应器这些反应器还必须适合 cGMP 工艺并且具有经济效率，以实现其实用性。总体而言，医疗保健系统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因此，我们将解决的未满足的需求是提供基于生物反应器的工作流程以实现高效。以患者特异性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、忠诚者和医疗保健经济。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。围绕降低其在精准医疗中的实用性风险并提高其在预期范围内的适用性和操作性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、强大的、生理相关的和临床预测性的大量未满足的需求和较低的进入职位门槛。总体而言，Link 的产品旨在实现可靠和稳健。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。