Type 1 Diabetes-A Proposal for Prevention & Intervention

描述（由申请人提供）：明尼苏达大学是美国最初的14个试验网中心之一。到目前为止，我们已经实施了8项协议。我们的优势在于预防和干预试验的招募，在这方面我们是排名第一的招募者。然而，我们在自然历史研究（NHS）的招聘情况一般。为了改善这一点，我们已经开始与凯文·彼得森博士进行新的合作，他是UM家庭医学和社区卫生部门的研究主任，也是明尼苏达家庭医生研究网络学院的主任。我们预计将立即为1000多名T1D患者提供服务，随着该网络的发展，未来的服务还会增加。

DESCRIPTION (provided by applicant): The University of Minnesota is one of the original 14 US TrialNet centers. We have implemented 8 protocols to date. Our particular strength has been enrollment in prevention and intervention trials, where we are the number 1 overall recruiter. Our recruitment in the Natural History Study (NHS), however, has been average. In order to improve this, we have embarked on a new collaboration with Dr. Kevin Peterson, Director of Research for the UM Department of Family Medicine and Community Health and Director of the Minnesota Academy of Family Physicians Research Network. We anticipate access immediately to more than 1000 patients with T1D, with increased future access as this network grows. In this application we are proposing therapy with autologous Tregulatory cells (Tregs). Previous protocols have attempted to increase endogenous Treg numbers with drugs. Tregs themselves have not previously been available in sufficient numbers for clinical use. Our group is the first to develop a clinically applicable selection and culture method for manufacturing large numbers of Tregs from peripheral blood. Preliminary data in animal models and in humans with leukemia suggest that this product is safe. This is a single site, single arm phase 1 dose escalation trial. Adult subjects with recent (3-12 months) onset T1D and persistent C-peptide secretion will receive an infusion of autologous peripheral blood- derived Tregs (CD4+/CD25+/FoxP3+) using new methodology developed at the UM Molecular and Cellular Therapeutics cGMP Facility. Cells will be collected by leukapheresis and expanded in culture for up to 35 days and then cryopreserved. Immediately following leukapheresis, subjects will receive a course of thymoglobulin, 4 doses over 1 week. Thawed, autologous Tregs will be infused approximately 2 months later, at a time when there is no residual detectable rabbit antibody in the circulation. Safety and immunologic data and C-peptide secretion will be followed for 2 years. The long-term goal is to gather preliminary data in anticipation of an intervention trial of peripheral-blood derived autologous CD4+/CD25+/FoxP3+ treatment of new onset T1D.