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.
Public Health Relevance Statement: NARRATIVE New and effective medical countermeasures are needed to protect victims of accidental radiation exposure or nuclear attack. These victims are highly susceptible to infections and uncontrolled bleeding due to injury to the blood forming components of bone marrow. Ossium Health is developing a readily deployable bank of cells that can form all blood components as a supportive therapy for victims of mass casualty radiation exposure events as well as conventional uses for blood cancer patients.
Project Terms: Ablation; Address; Agreement; Allogenic; animal rule; Animals; Antibodies; Antibody-drug conjugates; Area; base; biodosimetry; Biological Assay; Blood; Blood Platelets; bone; Bone Marrow; Bone Marrow Purging; Businesses; Cancer Patient; Caring; CD34 gene; cell bank; Cell Separation; Cell surface; Cell Therapy; Cells; Cellular Structures; Cessation of life; Clinical; Colony-Forming Units Assay; Complement; conditioning; cost; Cryopreservation; Cyclic GMP; cytokine; cytotoxic; Devices; Dose-Rate; Engraftment; Ensure; Evaluation; Event; Exposure to; FDA approved; Flow Cytometry; Funding; Future; graft vs host disease; Health; hematopoietic cell transplantation; Hematopoietic Neoplasms; Hematopoietic stem cells; Hemorrhage; high risk; HLA Antigens; Ice; In Vitro; in vivo; Individual; Infection; Infection prevention; infection risk; Infectious Agent; Injury; Intervention; Ionizing radiation; Lead; Leukopenia; Licensure; Major Histocompatibility Complex; mass casualty; Medical; medical countermeasure; metropolitan; Modeling; Mus; Myeloid Progenitor Cells; National Institute of Allergy and Infectious Disease; Natural Immunity; Neutropenia; neutrophil; New York City; novel; Nuclear; Nuclear Warfare; optimal treatments; Organ Donor; Organ Procurements; Pancytopenia; Patients; Pharmaceutical Preparations; Phase; phase 1 study; Population; pre-clinical; prevent; Procedures; Process; process optimization; Production; programs; Proto-Oncogene Protein c-kit; Qualifying; Radiation; Radiation Dose Unit; radiation effect; Radiation exposure; Radiation Injuries; Radiation Protection; Radiation therapy; Radiation Toxicity; Reagent; Recombinant Cytokines; reconstitution; Regimen; Registries; Reporting; Research; Risk; Safety; scale up; Ships; Source; stem cells; success; Supportive care; System; T-Lymphocyte; Technology; Testing; Thrombocytopenia; Tissue Donations; Transplantation; Treatment Protocols; Washington; Wood material; Work; Xenograft procedure
