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.

项目摘要 尽管嵌合抗原受体（CAR）-T细胞疗法针对肿瘤的临床成功，但 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）高达一百万美元的一半治疗成本； （ii）注入CAR-T细胞的数周或数月的延迟 疾病快速发展的患者； （iii）异质组成和终端分化 限制了CAR-T细胞植入和持久性的离体培养物，注入了CAR-T细胞。尽管 在这个领域取得的重大成就，减少时间，成本和监管负担仍然是一个深刻的未满足 CAR-T细胞疗法的需求以及显着的减少或消除离体过程仍然是一个关键 需要。该提案中概述的研究开发了新的生物材料方法来减少时间和精力 在体外产生CAR-T细胞，以增强CAR-T细胞表型和功能。我们提出了一小段（〜小时） 抗CD3/CD28抗体的前激活步骤可以立即进行转导和传递 使用生物材料支架。这种多样性补充将支持Trey Davis博士，并允许他参加 新实验扩展了AIM 1研究的范围，并将使他能够接受相关的强大培训 技术，专业发展和职业计划。我们希望我们的结果将为 一般的细胞治疗策略并促进广泛的患者访问，尤其是对拥有的人群 成为健康差异的受害者。