Reducing a major cost burden of therapeutic cell manufacturing by selectivelyremoving toxic culture byproducts to allow recycling of media

通过选择性去除有毒培养物副产物以允许介质回收，减少治疗细胞制造的主要成本负担

• 批准号: 10325616
• 负责人: Emily Hopewell
• 金额: $ 22.45万
• 依托单位: OSSIUM HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2023-07-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325616
• 关键词: Address; Adsorption; Allogenic; Amino Acids; Ammonia; Ammonium; Animal Disease Models; Area; Automobile Driving; Back; Blood Platelets; Bone Marrow; Buffers; Carbon; Cell Culture Techniques; Cell Therapy; Cells; Cellulose; Characteristics; Chemistry; Clinical; Clinical Medicine; Collaborations; Complex; Complex Analysis; Consumption; Culture Media; Data; Development; Devices; Dose; Economics; Equilibrium; Excision; Face; Filtration; Frequencies; Future; Goals; Growth; Growth Factor; Health; Human; Immunotherapy; Indiana; Kinetics; Lactic acid; Licensing; Measures; Mesenchymal Stem Cells; Metabolic; Methods; Modeling; Nutrient; Organ Donor; Penetration; Performance; Plant Resins; Porosity; Production; Recycling; Regenerative Medicine; Resources; Serum; Source; Sugar Acids; Supplementation; Surface; System; Technology; Testing; Therapeutic; Tissue Donors; Universities; Vertebral Bone; Waste Products; Work; base; bone; cell bank; cell growth; cell type; cost; cost effective; cytokine; design; economic impact; efficacy testing; gene therapy; large scale production; manufacturing scale-up; medical schools; preservation; programs; prototype; sensor; success; wasting

ABSTRACT: The tremendous cost of cell-based therapies manufacturing is the significant threat to the success of cell/gene therapy treatments. The cell culture medium alone can contribute to around 30-40% of the Cost of Goods (COGs). This is because, the current cell culture methods require frequent and complete media replacement in order to remove toxic metabolites from culture. This practice of completely replacing the medium with fresh medium adds significant expense and contributes to unnecessary waste. Restoring nutrient, osmotic, and pH balance need not require replacement of the entire culture medium volume. At production scale, some version of medium recycling will be required to reduce waste and overall cost of manufacturing. The aim of the current study is to develop a cost-effective media filtration system using coconut-shell derived activated carbons (CS-AC) that can selectively remove two important toxic metabolites such as lactic acid and ammonium from cell culture medium. With such filtration system, metabolic waste products can selectively be removed, non- metabolized components like buffers, and growth factors can be retained, and the depleted nutrients like sugars and amino acids can be replenished as they are consumed by the cells. Determining the level of recycling that is achievable by this filtration technology for each component of the culture medium requires a significantly more complex analysis informed by empirical data from spent medium analysis. The ultimate goal of this study is to utilize this filtration technology and develop a commercial grade single-use filtration device by embedding the AC into cellulose matrix or neutral-grade resins. The application of the new filtration device to remove toxic metabolites from spent culture medium will transform the current approaches being investigated for COG reduction during cell based therapeutic manufacturing. Such a filtration system holds a great promise for affordable cell/gene therapy treatment possibilities, and is expected to have a strong economical impact on clinical medicine.

抽象的： 细胞疗法制造的巨大成本是对成功的重大威胁 细胞/基因治疗。仅细胞培养基就可以贡献约 30-40% 的成本 货物 (COG)。这是因为，当前的细胞培养方法需要频繁且完整的培养基 更换以从培养物中去除有毒代谢物。这种完全替代媒介的做法 使用新鲜培养基会增加大量费用并造成不必要的浪费。恢复营养、渗透压、 pH 平衡不需要更换整个培养基体积。在生产规模上，一些 将需要介质回收版本以减少浪费和总体制造成本。该组织的目标是 目前的研究是使用椰壳活性炭开发一种具有成本效益的介质过滤系统 （CS-AC）可以选择性地去除水中两种重要的有毒代谢物，例如乳酸和铵 细胞培养基。有了这样的过滤系统，代谢废物可以选择性地被去除，非 缓冲液和生长因子等代谢成分可以被保留，而糖等消耗的营养物质可以被保留 氨基酸可以在被细胞消耗时得到补充。确定回收水平 通过这种过滤技术可以实现，对于培养基的每种成分来说，需要更多的 根据废介质分析的经验数据进行复杂的分析。 本研究的最终目标是利用这种过滤技术并开发商业级 将活性炭嵌入纤维素基质或中性级树脂中的一次性过滤装置。应用 从用过的培养基中去除有毒代谢物的新型过滤装置将改变当前的 正在研究在细胞治疗制造过程中减少 COG 的方法。这样的过滤 系统为负担得起的细胞/基因治疗的可能性提供了巨大的希望，并且预计将具有 对临床医学产生巨大的经济影响。