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是一家新兴的初创公司，旨在降低不断上升的医疗成本。处方药 成本是增长最快的组成部分，也是导致 医疗保健成本。制药和生物技术的全球焦点现在集中在两个领域：1) 生物制药的开发和生产以及2)细胞疗法。细胞疗法有 展示了改变癌症和其他衰弱疾病的治疗的巨大希望 疾病，FDA已经批准它们用于治疗白血病和 淋巴瘤。然而，一些细胞疗法的每次治疗费用超过35万美元，这使得 这些挽救生命的技术对许多患者来说是无法获得的。这项建议的目的是 展示一种简单有效的细胞增殖和细胞耗尽方法的可行性 通常在细胞治疗中使用。 我们对SBIR奖项第一阶段的短期目标是验证我们可以丰富T 以淋巴细胞为起始材料利用一种新型、无抗体的方法制造CAR T细胞 基于专利蛋白质技术和核酸适配子的分离平台 免疫亲和力捕获表达分化簇(CD)标记蛋白的细胞 CD_4。该平台将使用与核酸适配子共价连接的二氧化硅结合肽 识别一种感兴趣的细胞表面蛋白。由此产生的多肽-适配子嵌合体将 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 避免在抗体或其他蛋白质被共价修饰的情况下具有挑战性和昂贵的步骤 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。 当商业化后，这种方法将缓解对当前 技术--如成本高、开发周期长、缺乏自动化、复杂、 多步化学。利用Proteios平台开发细胞分离产品 有可能将细胞浓缩的成本降低十倍以上。此外，这一点 技术可以改变治疗性细胞的生产过程，以制造拯救生命的细胞 为更多的个人提供治疗方法。