Core B - Cell Engineering and Manufacturing Facility

核心 B - 电池工程和制造设施

• 批准号: 10713204
• 负责人: DONALD Lawrence SIEGEL
• 金额: $ 46.91万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713204
• 关键词: Accreditation; Affinity; Allogenic; Antibodies; B-Lymphocytes; Biological Assay; Biological Products; Blood Component Removal; CAR T cell therapy; CD19 gene; CD34 gene; CRISPR/Cas technology; Cell Therapy; Cells; Cellular immunotherapy; Clinical; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communicable Diseases; Communities; Complement; Core Facility; Cryopreservation; Development; Diagnostic; Ensure; Formulation; Foundations; Future; Genes; Goals; Hematopoietic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Human; Immunize; Immunoglobulin Fragments; Infiltration; Institution; Investigational New Drug Application; Investments; Knock-out; Laboratories; Libraries; Llama; Lymphocyte; Malignant Neoplasms; Marrow; Mediating; Medicine; Methods; Multiple Myeloma; PTPRC gene; Pathology; Patients; Pennsylvania; Peripheral Blood Lymphocyte; Phage Display; Phase; Property; Protocols documentation; Public Health; Quality Control; Refractory; Relapse; Resources; Science; Solid; Source; T-Lymphocyte; Technology; Testing; Therapeutic; Universities; Vaccine Production; Validation; base editing; bench-to-bedside translation; cellular engineering; chimeric antigen receptor; chimeric antigen receptor T cells; design; experience; first-in-human; gene function; improved; innovation; laboratory development; manufacture; manufacturing facility; non-Hodgkin' s lymphoma patients; novel; peripheral blood; programmed cell death protein 1; receptor binding; stem cells

Core B Summary Core B comprises two interrelated laboratories: the Clinical Cell and Vaccine Production Facility (CVPF), a GMP- compliant cell manufacturing facility, and an associated Antibody Development Laboratory (ADL) that is devoted to the discovery and design of novel CAR-T constructs for use by P01-proposed projects. The CVPF is a Foundation for the Accreditation of Cellular Therapy (FACT)-accredited facility and is the only GMP-compliant cell manufacturing facility on the University of Pennsylvania campus providing the university community with integrated scientific, technical, and regulatory expertise to support manufacturing of biologics for in-human Phase I and II clinical trials. The ADL is new to this P01 renewal application and will support the three scientific projects by developing novel chimeric antigen receptor binding domains to complement those that are currently available to the projects. Core B has four specific aims. In Aim 1, the CVPF will support Project 1 by providing 3-day manufacturing, validation, and cryopreservation of CRISPR-mediated knockout of CD5 in CD19-directed CAR- T cells for use in a clinical trial for relapsed/refractory CLL and NHL patients. In Aim 2, the CVPF will support Project 2 by manufacturing, validating, and cryopreserving CD45 base-edited CD34+ hematopoietic stem cells and CD45-directed CAR-T cells for use in a clinical trial for AML patients. In Aim 3, the CVPF will support Project 3 by manufacturing, validating, and cryopreserving BCMA-directed CAR-T cells from marrow infiltrating lymphocytes (MILs) for comparison with conventional peripheral blood-derived BCMA-directed CAR-T cells produced in parallel for use in a clinical trial for multiple myeloma patients. In Aim 4, the ADL will use antibody phage display technology to construct and screen libraries derived from llamas immunized with CD5, CD45, and BCMA in order to isolate single-domain VHH antibody fragments optimized with respect to affinity and other desired functional properties as needed for use in Projects 1, 2, and 3.

核心B总结 核心 B 包括两个相互关联的实验室：临床细胞和疫苗生产设施 (CVPF)、GMP- 合规细胞制造设施，以及相关的抗体开发实验室 (ADL)，专门致力于 发现和设计供 P01 提议的项目使用的新型 CAR-T 结构。 CVPF 是一个 获得细胞治疗认证基金会 (FACT) 认证的机构，是唯一符合 GMP 要求的机构 宾夕法尼亚大学校园内的细胞制造设施为大学社区提供 综合科学、技术和监管专业知识，支持人体阶段生物制剂的制造 I 和 II 临床试验。 ADL 是 P01 续签申请的新内容，将支持三个科学项目 通过开发新的嵌合抗原受体结合域来补充目前可用的那些 到项目。核心 B 有四个具体目标。在目标 1 中，CVPF 将通过提供为期 3 天的时间来支持项目 1 CD19 定向 CAR 中 CRISPR 介导的 CD5 敲除的制造、验证和冷冻保存 T 细胞用于复发/难治性 CLL 和 NHL 患者的临床试验。在目标 2 中，CVPF 将支持 项目2：制造、验证和冷冻保存CD45碱基编辑的CD34+造血干细胞 CD45 定向 CAR-T 细胞用于 AML 患者的临床试验。在目标 3 中，CVPF 将支持项目 3 通过制造、验证和冷冻保存来自骨髓浸润的 BCMA 定向 CAR-T 细胞 淋巴细胞 (MIL) 与传统外周血来源的 BCMA 定向 CAR-T 细胞进行比较 并行生产用于多发性骨髓瘤患者的临床试验。在目标 4 中，ADL 将使用抗体 噬菌体展示技术构建和筛选源自用 CD5、CD45 和免疫的美洲驼的文库 BCMA 用于分离单域 VHH 抗体片段，并在亲和力和其他方面进行了优化 项目 1、2 和 3 中使用所需的功能属性。