Core B: GMP Cell and RNA Manufacturing

摘要核心B：GMP细胞和RNA制造 核心B是临床细胞和疫苗生产设施(CVPF)。CVPF是 细胞疗法(FACT)认证-认可的、符合GMP(GMP)规范的细胞和 核糖核酸制造设施。这一设施支持将创新的调查结果翻译到床边。 适用于多种癌症、传染病和其他治疗适应症的细胞和基因生物制剂 宾夕法尼亚大学(宾夕法尼亚大学)及其合作机构。CVPF支持制造 18个正在研究的新药申请(IND)，并已生产了2400多个细胞疫苗，这些疫苗已被 安全地给900多名患者使用。CVPF被指定为核心B GMP细胞和RNA 本建议书中概述的项目的制造资源，并支持a)工艺开发和 成功的GMP临床翻译细胞和RNA制造的验证实验和b)临床 用于人类管理的转基因细胞的试制和最终产品测试。CVPF将 通过制定制造议定书为拟议项目提供具体支持(1) 串联CD19 CAR T细胞和CD22 CAR T细胞产物，(2)TCR阴性，HLA-I阴性CD19 CAR T CD33阴性的造血干细胞和CD33CAR T细胞，以及(4)串联的CD19CAR T细胞 和BCMA汽车T细胞产品。为了实现有效删除上述目标(TCR，人类白细胞抗原-I， CD33)，我们将生产GMP级的引导RNA和Cas9 mRNA。我们将电击穿治疗细胞 用这些RNA构建物来产生CRISPR/Cas9介导的靶向阴性细胞。质量控制分析和 将为每种治疗细胞类型制定释放标准，以确保安全和 高质量的修饰细胞。

SUMMARY CORE B: GMP CELL and RNA MANUFACTURING Core B is the Clinical Cell and Vaccine Production Facility (CVPF). The CVPF is a Foundation for the Accreditation of Cellular Therapy (FACT)-accredited, Good Manufacturing Practices (GMP) compliant cell and RNA manufacturing facility. This facility supports “bench to bedside” translation of innovative investigational cell and gene biologics for a wide range of cancers, infectious diseases, and other therapeutic indications at the University of Pennsylvania (Penn) and its collaborating institutions. The CVPF supports manufacturing for 18 investigational new drug applications (INDs), and has produced over 2400 cellular vaccines that have been safely administered to more than 900 patients. The CVPF is designated as the Core B GMP cell and RNA manufacturing resource for the projects outlined in this proposal, and supports a) process development and validation experiments for successful GMP clinical translation of cell and RNA manufacturing and b) clinical trial manufacturing and final product testing of gene modified cells for human administration. The CVPF will provide specific support for the proposed projects through the development of protocols to manufacture (1) tandem CD19 CAR T cell and CD22 CAR T cell products, (2) TCR negative, HLA-I negative CD19 CAR T cells, (3) CD33 negative hematopoietic stem cells and CD33 CAR T cells, and (4) tandem CD19 CAR T cell and BCMA CAR T cell products. To achieve effective deletion of the above mentioned targets (TCR, HLA-I, CD33) we will manufacture GMP-grade guide RNAs and Cas9 mRNA. We will electroporate therapeutic cells with these RNA constructs to create CRISPR/Cas9 mediate, target negative cells. Quality control assays and release criteria will be developed for each therapeutic cell type to ensure consistent production of safe and high quality modified cells.