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

基本信息

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
项目类别：
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

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

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项目摘要

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-Collaborative U01。联系PI -Gary Yam 项目摘要由于角膜疤痕引起的角膜失明会影响全球数百万的人。角膜移植是有效但有局限性。该多PI项目的目的是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。该项目的工作范围是验证和确认生成良好制造实践（GMP）干细胞的程序，验证细胞安全性，并分析针对基于细胞的角膜疤痕疾病的临床数据。山药实验室和已故詹姆斯·L（James L. Funderburgh已确认人角膜基质干细胞（CSSC）在动物中的再生作用角膜疤痕的模型。 HSU实验室和免疫学监测和蜂窝产品实验室（IMCPL）在UPMC Hillman癌症中心建立调查新药方面有丰富的经验（IND）制造程序，质量保证系统和文档以支持GMP单元产品 FDA注册临床试验的制造和处理。该提议是两者的联合力量在将来的临床试验和临床应用中，专业知识铺平了基于干细胞疗法的途径角膜疤痕。特定目标1将建立GMP等级的化学和制造控制（CMC） CSSC用于调查新药（IND）的CSSC。我们将表征和比较 GMP的质量提高了CSSC和实验室生成的细胞，并建立了完整的GMP生产方案。具体目标2将阐明GMP-CSSC的药理和毒理学作用。我们将研究细胞使用我们已建立的小鼠角膜损伤模型的安全性和功效，并将确定CSSC分布，代谢，吸收，排泄，代谢和肿瘤性。特定目标3将运行临床数据挖掘和将未来临床试验设计的分析。我们将使用角膜进行回顾性数据分析在UMPC眼中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有关患者资格和治疗结果分析的临床试验设计。该项目是根据我们可靠的基本和翻译研究和数据，并将导致建立GMP级CSSC准备临床试验并设计用于治疗角膜失明的临床试验。