Core B: GMP Cell and RNA Manufacturing

核心B总结：GMP细胞和RNA酶 核心B是临床细胞和疫苗生产设施（CVPF）。CVPF是一个基金会， 细胞治疗认证（FACT）-认证，符合良好生产规范（GMP）的细胞和 RNA制造工厂。该设施支持创新研究的“从实验室到床边”转化， 细胞和基因生物制剂，用于广泛的癌症、传染病和其他治疗适应症， 宾夕法尼亚大学及其合作机构。CVPF支持以下产品的制造 18项研究性新药申请（IND），并已生产了2400多种细胞疫苗， 安全地给900多名患者使用。CVPF被指定为核心B GMP细胞和RNA 本提案中概述的项目的制造资源，并支持a）工艺开发和 用于细胞和RNA制造的成功GMP临床翻译的验证实验，和B）临床 用于人类给药的基因修饰细胞的试生产和最终产品测试。CVPF将 通过制定制造协议，为拟议项目提供具体支持（1） 串联CD 19 CAR T细胞和CD 22 CAR T细胞产物，（2）TCR阴性、HLA-I阴性CD 19 CAR T细胞 细胞，（3）CD 33阴性造血干细胞和CD 33 CAR T细胞，和（4）串联CD 19 CAR T细胞 和BCMA CAR T细胞产品。为了实现上述靶标（TCR，HLA-I， CD 33），我们将生产GMP级指导RNA和Cas9 mRNA。我们将电穿孔治疗细胞 使用这些RNA构建体来创建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放行标准，以确保安全和 高质量的改良细胞。

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.