Simple and Effective Method for Cell Enrichment and Cell Depletion During Cell Therapy

细胞治疗过程中细胞富集和细胞去除的简单有效方法

• 批准号: 10045040
• 负责人: Bob Snyder
• 金额: $ 5.5万
• 依托单位: PROTEIOS TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10045040
• 关键词: Affinity; Amino Acids; Antibodies; Antineoplastic Agents; Area; Automation; Award; Binding; Biological Products; Biological Response Modifier Therapy; Biomanufacturing; Biotechnology; CD4 Antigens; CD8B1 gene; Cell Separation; Cell Surface Proteins; Cell Therapy; Cell surface; Cells; Chemistry; Chimera organism; Clinical; DNA Damage; Development; Differentiation Antigens; Disease; Drug Industry; Epitopes; Generations; Goals; Health Care Costs; Immune; Individual; Industry; Legal patent; Life; Ligation; Link; Lysine; Magnetism; Maleimides; Malignant Neoplasms; Manufacturer Name; Methods; Nucleic Acids; Patients; Peptide aptamers; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacy facility; Phase; Process; Production; Property; Proteins; Reaction; Reactive Oxygen Species; Reagent; Research; Research Personnel; Route; Savings; Silicon Dioxide; Small Business Innovation Research Grant; Sulfhydryl Compounds; System; T-Lymphocyte; Techniques; Technology; Therapeutic; Therapeutic procedure; Time; aptamer; base; cancer therapy; cell injury; chimeric antigen receptor T cells; cost; cost effective; interest; leukemia treatment; leukemia/lymphoma; magnetic beads; novel; oxidative damage; precision drugs; prescription drug costs; product development; protein purification; scale up; small molecule; sortase

Proteios is an emerging startup driven to reduce the rising cost of healthcare. Prescription drug costs are the fastest rising component and are contributing to the dramatic increase in healthcare costs. The worldwide focus of pharmacy and biotechnology is now in two areas: 1) biopharmaceutical development and production and 2) cell therapies. Cell therapies have demonstrated enormous promise for transforming the treatment of cancer and other debilitating diseases, and the FDA has already approved their use for the treatment of leukemia and lymphoma. However, some cell therapies cost over $350,000 per treatment, which has made these life-saving technologies inaccessible to many patients. The objective of this proposal is to show feasibility of a simple and effective method for cell enrichment and cell depletion commonly used during cell therapy. Our short-term goal for Phase I of the SBIR award is to validate that we can enrich T lymphocytes as starting material for CAR T cell manufacturing using a novel, antibody-free isolation platform based on proprietary protein technology and nucleic acid aptamers by immunoaffinity capture of cells that express the Cluster of Differentiation (CD) marker protein CD4. The platform will use a silica-binding peptide covalently linked to a nucleic acid aptamer that recognizes a cell surface protein of interest. The resulting peptide-aptamer chimera will reversibly bind cells to silica, an abundant, non-toxic, and inexpensive material. Our approach avoids challenging and costly steps where antibodies or other proteins are covalently modified to bind to beads or small molecules. Additionally, our approach eliminates commonly used reagents that cause oxidative damage to cells. When commercialized, this approach will alleviate some of the concerns with current technologies - such as high cost, long development times, lack of automation, and complicated, multistep chemistry. The development of products for cell isolation using the Proteios platform has the potential to reduce the cost of cell enrichments more than tenfold. Furthermore, this technology could transform the production process for therapeutic cells to make life-saving cell therapies available to more individuals.

Proteios是一家新兴创业公司，旨在降低医疗保健成本上升。处方药 成本是最快的上升组成部分，并有助于急剧增加 医疗保健费用。药房和生物技术的全球重点现在在两个领域：1） 生物药物的发育和生产以及2）细胞疗法。细胞疗法具有 在转化癌症和其他衰弱的治疗方面表现出了巨大的希望 疾病，FDA已经批准用于治疗白血病和 淋巴瘤。但是，某些细胞疗法的每次治疗费用超过35万美元，这已经使 这些挽救生命的技术对许多患者无法访问。该提议的目的是 显示出一种简单有效的细胞富集和细胞耗竭方法的可行性 通常在细胞疗法中使用。 我们SBIR奖第一阶段的短期目标是验证我们可以丰富 淋巴细胞是使用新颖的，无抗体的汽车T细胞制造的起始材料 基于专有蛋白质技术和核酸适体的隔离平台 表达分化簇（CD）标记蛋白的细胞的免疫亲和力捕获 CD4。该平台将使用与核酸适体连接的二氧化硅结合肽 识别感兴趣的细胞表面蛋白。由此产生的肽 - 调节液将 可逆地将细胞与二氧化硅结合，二氧化硅是一种丰富，无毒和廉价的材料。我们的方法 避免在共价修改抗体或其他蛋白质的挑战和昂贵的步骤 与珠子或小分子结合。此外，我们的方法消除了常用的 对细胞造成氧化损伤的试剂。 当商业化时，这种方法将减轻当前的一些问题 技术 - 例如高成本，较长的开发时间，缺乏自动化和复杂的技术， 多步化学。使用Proteios平台开发用于细胞隔离的产品 有可能降低细胞富集成本超过十倍以上。此外，这个 技术可以改变治疗细胞制造挽救生命细胞的生产过程 疗法可供更多人使用。