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Core B: GMP Cell and RNA Manufacturing

核心 B：GMP 细胞和 RNA 制造

基本信息

批准号：
10245069
负责人：
DONALD Lawrence SIEGEL
金额：
$ 23.58万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10245069
关键词：
Accreditation Allogenic Anti-CD22 Autologous Biological Biological Assay Blood Component Removal CAR T cell therapy CD19 gene CD22 gene CRISPR/Cas technology Cancer Burden Cancer Center Cell Therapy Cells Clinical Clinical Trials Clustered Regularly Interspaced Short Palindromic Repeats Collection Communicable Diseases Communities Core Facility Cryopreservation Development Dose Ensure Foundations Gene-Modified Genes Goals Guide RNA Hematologic Neoplasms Hematopoietic Stem Cell Mobilization Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Human In Vitro Institution Investigation Investigational New Drug Application Laboratories Lentivirus Vector MS4A1 gene Malignant Neoplasms Mediating Medicine Messenger RNA Methods Mononuclear Pathology Patients Pennsylvania Peripheral Blood Stem Cell Phase I Clinical Trials Phase II Clinical Trials Process Production Protocols documentation Quality Control RNA Reagent Resources Surface T-Lymphocyte Testing Therapeutic Translations United States Universities Vaccine Production Vaccines Validation bench to bedside beta-2 Microglobulin cell type chimeric antigen receptor T cells clinical development clinical practice clinical translation design experimental study first-in-human innovation manufacturing facility manufacturing process pre-clinical protocol development scale up technology development

项目摘要

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.

核心摘要 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 是一个基金会细胞治疗认证 (FACT) 认可、符合良好生产规范 (GMP) 的细胞和 RNA 制造设施。该设施支持创新研究的“从实验室到临床”的转化用于多种癌症、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（Penn）及其合作机构。 CVPF 支持制造 18 项研究性新药申请 (IND)，并已生产超过 2400 种细胞疫苗已安全地对900多名患者进行了治疗。 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) 工艺开发和细胞和 RNA 制造的成功 GMP 临床转化的验证实验和 b) 临床用于人类施用的基因修饰细胞的试制和最终产品测试。 CVPF 将通过制定制造协议为拟议项目提供具体支持 (1) 串联CD19 CAR T细胞和CD22 CAR T细胞产品，（2）TCR阴性、HLA-I阴性CD19 CAR T 细胞，(3) CD33 阴性造血干细胞和 CD33 CAR T 细胞，以及 (4) 串联 CD19 CAR T 细胞和BCMA CAR T细胞产品。实现上述靶点（TCR、HLA-I、 CD33）我们将生产 GMP 级向导 RNA 和 Cas9 mRNA。我们将对治疗细胞进行电穿孔使用这些 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释放标准，以确保持续生产安全和高品质的修饰细胞。