Biomaterial Scaffolds for Ex Vivo and In Situ CAR-T Cell Production

用于离体和原位 CAR-T 细胞生产的生物材料支架

• 批准号: 10746676
• 负责人: Yevgeny Brudno
• 金额: $ 8.51万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-16 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10746676
• 关键词: Achievement; Antibodies; Biocompatible Materials; CAR T cell therapy; CD28 gene; CD3 Antigens; Cell Therapy; Cells; Clinical; Clinical Data; Cytotoxic T-Lymphocytes; Development; Disease Progression; Engraftment; Hematopoietic Neoplasms; Hour; Immune system; In Situ; In Vitro; Methods; Patients; Phenotype; Population; Procedures; Production; Public Health; Research; Specificity; Techniques; Time; Training; Translating; bioscaffold; career; chimeric antigen receptor; chimeric antigen receptor T cells; cost; experimental study; health disparity; improved; manufacture; manufacturing facility; manufacturing process; programs; success; tumor

PROJECT SUMMARY Despite unprecedented clinical success of chimeric antigen receptor (CAR)-T cell therapy against tumors, widespread application is limited by lengthy and labor-intensive ex vivo manufacturing procedures that result in: (i) very high costs of therapy of up to half of a million dollars; (ii) delays of weeks or months to infuse CAR-T cells to patients with rapidly progressing disease; and (iii) heterogeneous composition and terminal differentiation of infused CAR-T cells as a result of ex vivo culture that limit CAR-T cell engraftment and persistence. Despite significant achievements in this space, reducing the time, costs and regulatory burden remains a deep unmet need in CAR-T cell therapy and significant reducing or eliminating ex vivo procedures remains a critical unmet need. The research outlined in this proposal develops new biomaterials approaches to reduce the time and effort to produce CAR-T cells in vitro, to enhance CAR-T cell phenotype and function. We propose that a short (~hour) pre-activation step with anti-CD3/CD28 antibodies can be immediately followed by transduction and delivery using a biomaterial scaffold. This diversity supplement will support Dr. Trey Davis and allow him to participate in new experiments to extend the scope of Aim 1 studies and will allow him to receive robust training in associated techniques, professional development, and career planning. We expect that our results will provide a basis for a general cellular therapeutic strategy and promote widespread patient access, especially to populations that have been the victims of health disparities.

项目概要 尽管嵌合抗原受体（CAR）-T 细胞疗法在治疗肿瘤方面取得了前所未有的临床成功， 广泛的应用受到冗长且劳动密集型的离体制造程序的限制，这些程序导致： (i) 治疗费用极高，高达 50 万美元； (ii) CAR-T 细胞输注延迟数周或数月 疾病快速进展的患者； (iii)异质组成和终末分化 由于离体培养而输注的 CAR-T 细胞限制了 CAR-T 细胞的植入和持久性。尽管 在这一领域取得了重大成就，但减少时间、成本和监管负担仍然是一个尚未解决的问题 CAR-T 细胞疗法的需求以及显着减少或消除离体程序仍然是一个关键的未满足问题 需要。本提案中概述的研究开发了新的生物材料方法，以减少时间和精力 体外生产CAR-T细胞，增强CAR-T细胞表型和功能。我们建议短期（〜小时） 使用抗 CD3/CD28 抗体进行预激活步骤后可立即进行转导和递送 使用生物材料支架。该多样性补充品将支持 Trey Davis 博士并允许他参与 新的实验扩大了 Aim 1 研究的范围，并使他能够接受相关领域的强有力的培训 技术、专业发展和职业规划。我们期望我们的结果将为 一般的细胞治疗策略并促进广泛的患者获得，特别是对于患有这种疾病的人群 成为健康差距的受害者。