Cell Therapy Program with Scale-up cGMP Manufacturing of Human Corneal Stromal Stem Cells

细胞治疗计划，扩大人类角膜基质干细胞的 cGMP 生产

• 批准号: 10720562
• 负责人: Yen-Michael S. Hsu
• 金额: $ 53.44万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10720562
• 关键词: Advisory Committees; Affect; Allografting; Animal Model; Animals; Anti-Inflammatory Agents; Behavior; Biological Assay; Blindness; Cancer Center; Cell Therapy; Cells; Characteristics; Chemistry; Cicatrix; Clinic; Clinical Data; Clinical Protocols; Clinical Treatment; Clinical Trials; Clinical Trials Design; Cornea; Corneal Injury; Corneal Opacity; Cryopreservation; Cyclic GMP; Data; Data Analyses; Data Analytics; Databases; Disease; Documentation; Eligibility Determination; Environment; Etiology; Excretory function; Foundations; Future; Goals; Good Manufacturing Process; Graft Rejection; Human; Immunologic Monitoring; Investigation; Investigational Drugs; Joints; Keratitis; Keratoplasty; Laboratories; Manuals; Medical center; Metabolism; Modeling; Monitor; Multivariate Analysis; Mus; Natural regeneration; Operative Surgical Procedures; Ophthalmology; Outcome; Patients; Persons; Pharmacology and Toxicology; Phase; Postoperative Complications; Preparation; Procedures; Production; Protocols documentation; Qualifying; Quality Control; Rehabilitation therapy; Route; Running; Safety; Solid; System; Testing; Tissues; Topical application; Toxic effect; Toxicology; Translating; Transplantation; Treatment Efficacy; Treatment outcome; Tumorigenicity; Universities; Visit; Visual; Visual Acuity; Work; Wound models; Yam - dietary; absorption; clinical application; clinical trial readiness; clinically relevant; corneal allograft; corneal regeneration; corneal scar; dashboard; data mining; design; digital; efficacy testing; electronic health data; experience; eye center; healing; in vivo; indexing; innovation; manufacture; mouse model; novel therapeutics; ophthalmic examination; patient health information; pharmacologic; prevent; programs; quality assurance; regenerative; response; safety testing; scale up; stem cell based approach; stem cell therapy; stem cells; stemness; success; translational study; visual performance; welfare

RFA-HL-23-019 RMIP II-Collaborative U01. Contact PI - Gary Yam Project Abstract Corneal blindness due to corneal scarring affects millions of people worldwide. Corneal transplantation is effective but has limitations. This Multi-PI project is aimed to establish a new stem cell-based approach to reduce the need for corneal allograft transplantation. The scopes of work in this project are to validate and confirm procedures to generate Good Manufacturing Practice (GMP) stem cells, verify the cell safety, and analyze clinical data towards a cell-based therapy for corneal scarring disorders. The Yam Lab and the Corneal Task Force at the University of Pittsburgh, following the innovative work by the late James L. Funderburgh, have confirmed the regenerative effects of human corneal stromal stem cells (CSSC) in animal models of corneal scarring. The Hsu Lab and the Immunologic Monitoring and Cellular Products Laboratory (IMCPL) at UPMC Hillman Cancer Center have immense experience in establishing Investigation New Drugs (IND) manufacturing procedures, quality assurance systems and documentation to support GMP cell product manufacturing and processing for FDA-registered clinical trials. This proposal is a joint force of the two expertise to pave a route to stem cell-based therapy in future clinical trials and clinical applications treating corneal scarring. Specific Aim 1 will establish Chemistry and Manufacturing Control (CMC) for GMP grade CSSC for allocation towards Investigation New Drugs (IND) in FDA. We will characterize and compare the quality of GMP raised CSSC and lab-generated cells, and establish a complete GMP production protocol. Specific Aim 2 will elucidate the pharmacological and toxicological effects of GMP-CSSC. We will study cell safety and efficacy using our established mouse corneal injury model and will determine CSSC distribution, metabolism, absorption, excretion, metabolism, and tumorigenicity. Specific Aim 3 will run clinical data mining and analysis that will direct future clinical trial design. We will do retrospective data analysis using corneal keratitis and scarring patient database at the UMPC Eye Center and obtain statistical data to direct future clinical trial design on patient eligibility and treatment outcome analysis. This project is established based on our solid basic and translational studies and data, and will lead to establish GMP-grade CSSC ready for clinical trials and to design clinical trials for treating corneal blindness.

RFA-HL-23-019 RMIP II-协作U 01。联系PI -加里任 项目摘要 由于角膜瘢痕形成导致的角膜失明影响着全世界数百万人。角膜移植是 有效，但有局限性。该多PI项目旨在建立一种新的基于干细胞的方法， 减少对角膜同种异体移植的需求。本项目的工作范围是验证和 确认生成良好生产规范（GMP）干细胞的程序，验证细胞安全性，以及 分析临床数据，为角膜瘢痕形成疾病提供基于细胞的治疗。山药实验室和 匹兹堡大学的角膜工作组，继已故的詹姆斯L。 Funderburgh等人已经证实了人角膜基质干细胞（CSSC）在动物体内的再生作用。 角膜瘢痕模型。Hsu实验室和免疫监测和细胞制品实验室 （IMCPL）在UPMC希尔曼癌症中心有丰富的经验，建立研究新药 (IND)支持GMP细胞产品的生产程序、质量保证体系和文件 用于FDA注册的临床试验的生产和加工。这一建议是两者的合力 专业知识，为未来的临床试验和临床应用中的干细胞治疗铺平道路。 角膜疤痕具体目标1将建立GMP级化学和生产控制（CMC） CSSC用于分配给FDA的新药研究（IND）。我们将描述和比较 提高了CSSC和实验室生成细胞的GMP质量，并建立了完整的GMP生产规程。 具体目标2将阐明GMP-CSSC的药理学和毒理学作用。我们将研究细胞 安全性和有效性，并将确定CSSC分布， 代谢、吸收、排泄、代谢和致瘤性。Specific Aim 3将运行临床数据挖掘 和分析，将指导未来的临床试验设计。我们将使用角膜移植进行回顾性数据分析， UMPC眼科中心的角膜炎和瘢痕患者数据库，并获得统计数据，以指导未来的 患者合格性和治疗结局分析的临床试验设计。本项目是根据 我们坚实的基础和转化研究和数据，并将导致建立GMP级CSSC准备临床 设计治疗角膜盲的临床试验。