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

RFA-HL-23-019 RMIP II-协作U01。联系PI-Gary Yam 项目摘要 由于角膜疤痕造成的角膜失明影响着全球数百万人。角膜移植是 有效，但也有局限性。这个多PI项目旨在建立一种基于干细胞的新方法 减少同种异体角膜移植的需要。此项目的工作范围是验证和 确认生产良好制造规范(GMP)干细胞的程序，验证细胞安全性；以及 分析临床数据，以细胞为基础的治疗角膜疤痕疾病。山药实验室和 在已故的詹姆斯·L·李的创新工作之后，匹兹堡大学的角膜工作组。 证实了人角膜基质干细胞(CSSC)在动物体内的再生作用。 角膜疤痕模型。徐氏实验室和免疫监测及细胞产品实验室 UPMC Hillman癌症中心(IMCPL)在建立新药研究方面拥有丰富的经验 (IND)支持GMP单元产品的制造程序、质量保证体系和文件 FDA注册的临床试验的制造和加工。这项提议是两者的合力。 在未来的临床试验和临床应用治疗中为干细胞疗法铺平道路的专业知识 角膜上的疤痕。具体目标1将为GMP级别建立化学和制造控制(CMC) 用于FDA新药(IND)研究的CSSC。我们将描述和比较 提高了CSSC和实验室培养细胞的GMP质量，建立了完整的GMP生产流程。 具体目标2将阐明GMP-CSSC的药理和毒理作用。我们将研究细胞 安全性和有效性使用我们建立的小鼠角膜损伤模型，并将确定CSSC的分布， 代谢、吸收、排泄、新陈代谢和致瘤性。《特定目标3》将运行临床数据挖掘 以及将指导未来临床试验设计的分析。我们将使用Corneal进行回顾性数据分析 UMPC眼科中心的角膜炎和疤痕患者数据库，并获得统计数据以指导未来 关于患者资格和治疗结果分析的临床试验设计。这个项目是基于 我们扎实的基础和翻译研究和数据，并将导致建立GMP级CSSC准备临床 并设计治疗角膜失明的临床试验。

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.