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.

摘要核心B：GMP单元和RNA制造 Core B是临床细胞和疫苗生产设施（CVPF）。 CVPF是认可的细胞疗法（事实）认可的，良好的制造实践（GMP）兼容的细胞和 RNA制造设施。该设施支持创新调查的“长凳床头”翻译各种癌症，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个研究性新药应用（INDS），已经生产了超过2400多个细胞疫苗安全地给900多名患者。 CVPF被设计为核心B GMP单元和RNA 为本提案中概述的项目制造资源，并支持a）流程开发和用于成功GMP细胞和RNA制造的成功GMP临床翻译的验证实验和b）临床基因改性细胞的试验制造和最终产品测试用于人类给药。 CVPF会通过制定制造协议为拟议的项目提供特定的支持（1）串联CD19汽车T细胞和CD22 CAR T细胞产物，（2）TCR负，HLA-I负CD19 CAR T 细胞，（3）CD33阴性造血干细胞和CD33 CAR T细胞，（4）串联CD19 CAR T细胞和BCMA汽车T细胞产品。为了实现上述目标的有效删除（TCR，HLA-I， CD33）我们将生产GMP级指南RNA和Cas9 mRNA。我们将电动治疗细胞借助这些RNA构建体以创建CRISPR/CAS9介导，靶向负细胞。质量控制测定法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。