Developing a bank of purified myeloid progenitor cells as a bridging therapy for transient pancytopenia resulting from radiation injury

开发纯化的骨髓祖细胞库作为放射损伤引起的短暂性全血细胞减少症的桥接疗法

• 批准号: 10081134
• 负责人: Brian H. Johnstone
• 金额: $ 30万
• 依托单位: OSSIUM HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-18 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10081134
• 关键词: Ablation; Address; Agreement; Allogenic; Animals; Antibodies; Antibody-drug conjugates; Area; Biological Assay; Blood; Blood Platelets; Bone Marrow; Bone Marrow Purging; Businesses; CD34 gene; Cancer Patient; Caring; Cell Separation; Cell Therapy; Cell surface; Cells; Cellular Structures; Cessation of life; Clinical; Colony-Forming Units Assay; Complement; Cryopreservation; Cyclic GMP; Devices; Dose-Rate; Engraftment; Ensure; Evaluation; Event; Exposure to; FDA approved; Flow Cytometry; Funding; Future; HLA Antigens; Health; Hematopoietic Neoplasms; Hematopoietic stem cells; Hemorrhage; Ice; In Vitro; Individual; Infection; Infection prevention; Infectious Agent; Injury; Intervention; Ionizing radiation; Lead; Leukopenia; Licensure; Major Histocompatibility Complex; Medical; Modeling; Mus; Myeloid Progenitor Cells; National Institute of Allergy and Infectious Disease; Natural Immunity; Neutropenia; New York City; Nuclear; Nuclear Warfare; Organ Donor; Organ Procurements; Pancytopenia; Patients; Pharmaceutical Preparations; Phase; Population; Procedures; Process; Production; Proto-Oncogene Protein c-kit; Qualifying; Radiation; Radiation Dose Unit; Radiation Injuries; Radiation Protection; Radiation Toxicity; Radiation exposure; Radiation therapy; Reagent; Recombinant Cytokines; Regimen; Registries; Reporting; Research; Risk; Safety; Ships; Source; Supportive care; System; T-Lymphocyte; Technology; Testing; Thrombocytopenia; Tissue Donations; Transplantation; Treatment Protocols; Washington; Wood material; Work; Xenograft procedure; animal rule; base; biodosimetry; bone; cell bank; conditioning; cost; cytokine; cytotoxic; graft vs host disease; hematopoietic cell transplantation; high risk; in vivo; infection risk; mass casualty; medical countermeasure; metropolitan; neutrophil; novel; optimal treatments; phase 1 study; pre-clinical; prevent; process optimization; programs; radiation effect; reconstitution; scale up; stem cells; success

ABSTRACT Exposure to even moderate levels (<3 Gy) of ionizing radiation can result in severe pancyotopenia, placing patients as wells as victims of accidental exposure at high risks for infection and uncontrolled hemorrhaging. Accidental exposure differs from radiation therapy in that biodosimetry (e.g., type of radiation, dose and dose rate) is often uncertain; consequently, the optimal treatment regimen to ameliorate the effects of radiation is not immediately evident. Therefore, victims of accidental ionizing radiation exposure would benefit from bridging therapies to traverse extended periods of neutropenia and thrombocytopenia until the optimal course of medical care can be determined. Ossium Health proposes to develop a bank of myeloid progenitor cells (MPC) from deceased donor bone marrow (BM). The strategy employs commercially available immunomagnetic selection reagents and clinical-scale closed-system semi-automated devices to specific select MPC from whole BM based on defining cell surface markers CD34+CD38+. The proposed Phase I studies build on our previous success with selecting large numbers (>150 million) of stem and progenitor cells from organ donor BM. We will evaluate combinations of selection, depletion and ablation to purify MPC without contaminating T cells long-term repopulating stem cells to prevent graft versus host disease. The cells will be validated in vitro and in vivo in a mouse xenotransplantation study to evaluate reestablishment of short-term innate immunity. The overall product of this research program will be a compelling preclinical package to justify definitive studies to support FDA approval under the Animal Rule for a novel radiation/nuclear mass casualty medical countermeasure bridging therapy. Future commercial viability for both medical countermeasures and civilian uses is enhanced by the up to 5-fold lower cost for manufacturing compared to current technologies.

摘要