Induction of Donor Tolerance in Renal Transplants

描述(申请人提供)：骨髓移植(BMT)可以治疗镰状细胞性贫血、1型糖尿病、多发性硬化症等自身免疫性疾病，并在实体器官和细胞移植受者中诱导免疫耐受。然而，与骨髓移植相关的毒性和并发症，主要是移植物抗宿主病(GvHD)，限制了骨髓移植在治疗白血病等危及生命的疾病中的应用。我们的目标是推出一种定义明确的骨髓细胞处理程序，称为FCRx，它将支持在最小的患者条件下进行持久的骨髓移植植入，而不会在不匹配的受者中发生GvHD。我们已经确定，其他人已经证实，移植促进细胞(FC)的骨髓细胞群可以促进不相合受者的骨髓移植，而不会导致GvHD。FC的发现是一项重要的发现，因为它为使用骨髓移植作为非恶性疾病的标准治疗打开了大门。提议的商业化进程，FCRx。将产生一种生物工程骨髓移植，其中包括造血干细胞(HSC)和促进细胞(FC)，但不包括有害的T细胞。 我们建议在第一阶段进行概念验证的具体目标如下：FCRx生产的移植物将在FDA批准的联合肾脏和骨髓移植的临床试验中进行测试，其最终目标是诱导免疫耐受，从而消除或减少对昂贵和有害的免疫抑制药物的需求。在Aim I中，我们将证明专利程序可以常规地生产具有特定规格的干细胞、促进细胞和aa3TCR+细胞的移植物。通过FCRx工艺进行嫁接生产的重复性和质量保证将使其成功投入商业运行。在AIM II中，我们将测试这一过程将产生骨髓移植移植物的假设，该移植物将实现高度不相合的供者干细胞在移植受者体内的植入，而不会导致显着的GVHD。Regenerex，LLC是一家女性所有的企业，位于EPSCoR州肯塔基州。

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.