The overall goal is to develop human allogeneic Megakaryocyte Progenitors (MKP, designated CL T-009) as a cell therapeutic to treat radiation induced thrombocytopenia in cancer patients. Thrombocytopenia is a common dose-limiting toxicity of radiotherapy in cancer patients resulting in treatment interruptions as well as increased risk of life-threatening bleeding complications. The interruption of radiotherapy due to thrombocytopenia or inability to complete cycles of chemo/radiation regimens results in decreased control of tumors and hinders potentially curative treatments for patients. Growth factor-based approaches have not had success and therapy to minimize the depth and duration of thrombocytopenia in cancer patients is an unmet need. Successful development of such a therapy reduces the risk of life threatening bleeding events and enables completing treatment regimens with potentially greater efficacy for the patient. Previous work at Cellerant has demonstrated the successful production of MKP at the research level that are able to produce human platelets in irradiated rodent xenograft models in vivo with funtionality similar to normal human platelets in ex vivo platelet activation assays. The specific aims of this proposal are to develop culture methods and assays for the expansion, characterization and production of sufficient quality and quantity MKP to initiate and complete IND enabling studies. This includes optimizing media formulations, growth and culturing conditions and scalability of production of MKP for preclinical efficacy, safety and related IND studies, ultimately leading to enablement of GMP manufacture of CL T-009 for clinical trial use.
