DEVELOPMENT OF PLX-R18 CELL THERAPY AS A COUNTERMEASURE FOR HEMATOPOIETIC ACUTE RADIATION SYNDROME

开发 PLX-R18 细胞疗法作为造血急性辐射综合征的对策

• 批准号: 10932592
• 负责人: CHEN FRANCO-YEHUDA
• 金额: $ 144.51万
• 依托单位: PLURISTEM, LTD
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10932592
• 关键词: Animal Model; B-Lymphocytes; Biological Assay; Biotechnology; C57BL/6 Mouse; Cell Therapy; Cells; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Contractor; Controlled Study; Development; Dose; Failure; Future; Goals; Hematopoietic; Hour; Human; In Vitro; Licensure; Patients; Placenta; Prevention; Production; Radiation; Radiation Toxicity; Radiation exposure; Radiobiology; Research Institute; Rodent; Sampling; Stromal Cells; Treatment Protocols; Whole-Body Irradiation; animal rule; cytokine; design; efficacy evaluation; efficacy study; in vivo; manufacture; migration; novel; response; single cell analysis; transcriptome sequencing

The goal of this proposal is to develop human placenta-derived stromal cells, PLX-R18 cell therapy, for mitigation of H-ARS. Pluri Biotech’s main subcontractor is the Armed Forces Radiobiology Research Institute, and the Offeror proposes extensive in vitro characterization and production of CRISPR-modified cells, as well as irradiated rodent and NHP product efficacy studies. The Contractor shall perform studies to support the development of PLX-R18 as a novel cellular MCM for the prevention, mitigation, and treatment of all aspects of H-ARS. Studies will evaluate the efficacy and mechanism of action of PLX-R18 in vitro and in animal models of H-ARS, when administered at least 24 hours after radiation exposure. This project is expected to deliver all information required to justify and design future adequate and well-controlled studies to support licensure of PLX-R18. Importantly, the proposed study aims to demonstrate efficacy of PLX-R18 even when administered 48 hours or later after radiation exposure. In addition, the Contractor shall perform the necessary regulatory steps towards FDA approval under the US FDA Animal Rule.

该提案的目标是开发人胎盘源性基质细胞PLX-R18细胞疗法，用于缓解H-ARS。Pluri Biotech的主要分包商是武装部队放射生物学研究所，要约人提出了CRISPR修饰细胞的广泛体外表征和生产，以及辐照啮齿动物和NHP产品功效研究。承包商应进行研究，以支持PLX-R18作为新型蜂窝MCM的开发，用于预防、缓解和治疗H-ARS的各个方面。研究将在体外和H-ARS动物模型中评价PLX-R18在辐射暴露后至少24小时给药的疗效和作用机制。该项目预计将提供证明和设计未来充分和良好对照研究所需的所有信息，以支持PLX-R18的许可。重要的是，拟议的研究旨在证明PLX-R18的疗效，即使在辐射暴露后48小时或更晚给药。此外，承包商应根据美国FDA动物法规执行必要的监管步骤，以获得FDA批准。