Induction of Donor Tolerance in Renal Transplants

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DESCRIPTION (provided by applicant): Bone marrow transplantation (BMT) can treat sickle cell anemia, type 1 diabetes, multiple sclerosis and other autoimmune disorders, and induces immune tolerance in solid organ and cell transplant recipients. However, the toxicity and complications associated with BMT, primarily graft versus host disease (GvHD), limit the therapeutic application of BMT to treatment of life threatening disorders, such as leukemia. Our goal is to market a well-defined bone marrow cell processing procedure, called FCRx, that will support durable bone marrow transplant engraftment following minimal patient conditioning, without GvHD in mismatched recipients. We have identified, and others have confirmed, a bone marrow cell population of graft facilitating cells (FC) that facilitates engraftment of marrow in mismatched recipients without causing GvHD. The discovery of FC is an important finding as it opens the door to employing BMT as a standard therapy for nonmalignant conditions. The process proposed for commercialization, FCRx. will produce a bioengineered bone marrow graft that includes hematopoietic stem cells (HSC) and facilitating cells (FC), but excludes harmful T cells. We propose the following specific aims for proof-of-concept in Phase I. The FCRx-produced graft will be tested in an FDA-approved clinical trial involving combined kidney and BMT whose ultimate goal is the induction of immune tolerance and the consequent elimination of or reduction in the need for expensive and harmful imrnunosuppressive drugs. In Aim I we will demonstrate that the proprietary procedure can routinely produce a graft with defined specifications for stem cells, facilitating cells and aa3TCR+ cells. The reproducibility and quality assurance of graft production through the FCRx process will lead to its successful commercial launch. In Aim II we will test the hypothesis that this process will produce a BMT graft that will achieve engraftment of highly HLA mismatched donor stem cells in transplant recipients without causing significant GVHD. Regenerex, LLC is a woman-owned business located in Kentucky, an EPSCoR state.