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B-Lymphocyte Immunotherapy in Islet Transplantation

胰岛移植中的 B 淋巴细胞免疫治疗

基本信息

批准号：
8141988
负责人：
Ali Naji
金额：
--
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2012-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Islet transplantation can restore endogenous insulin secretion in patients with type 1 diabetes (T1D) and consequently enable the attainment of near-normal glycemic control in the absence of severe episodes of hypoglycemia. At the University of Pennsylvania, we have been investigating the efficacy of combined B- and T- lymphocyte directed immunotherapy for promoting immunological tolerance to islet allografts in TID patients (CIT 05). We are also participating in the phase 3 FDA registration trial investigating a T-cell directed immunotherapy (CIT 07), and the islet-after-kidney (lAK) trial in T1D subjects following successful renal transplantation (CIT 06). Penn actively participated in the development of the Consortium Standard Operating Procedures using Serva collagenase in islet manufacturing. Penn became the first center to qualify to proceed with islet transplantations in 2008, and in that year performed three clinical transplants using single islet donors. The initiation of clinical islet transplantation provided the unique opportunity to utilize metabolic and immunologic mechanistic studies to gain insight into beta cell secretory capacity and immunological alterations in lymphocyte phenotype and function after islet transplantation, respectively. Having achieved these milestones of islet manufacturing and transplantation, we are committed to completing the Consortium clinical trials and the accompanying metabolic and immunologic studies. RELEVANCE: Type 1 diabetes (T1 D) results from the selective loss of insulin-producing beta cells in pancreatic islets. Despite a multitude of advanced insulin delivery systems, subjects with TID continue with abnormal fluctuations in glucose level, leading to the development of secondary complications of the disease. Islet transplantation has the potential to provide precise and long term control of glucose metabolism, thus preventing secondary complications of the disease.

描述（由申请人提供）：胰岛移植可以恢复1型糖尿病（T1 D）患者的内源性胰岛素分泌，从而在没有严重低血糖发作的情况下实现接近正常的血糖控制。在宾夕法尼亚大学，我们一直在研究联合B-和T-淋巴细胞定向免疫疗法促进TID患者对胰岛同种异体移植物免疫耐受的疗效（CIT 05）。我们还参与了研究T细胞定向免疫疗法的3期FDA注册试验（CIT 07），以及在成功肾移植后的T1 D受试者中进行的肾后胰岛（IAK）试验（CIT 06）。Penn积极参与了在胰岛生产中使用Serva胶原酶的联盟标准操作规程的开发。宾夕法尼亚大学在2008年成为第一个有资格进行胰岛移植的中心，并在那一年使用单个胰岛供体进行了三次临床移植。临床胰岛移植的开始提供了独特的机会，利用代谢和免疫机制的研究，以深入了解胰岛移植后的β细胞分泌能力和淋巴细胞表型和功能的免疫学改变。在实现了胰岛制造和移植的这些里程碑之后，我们致力于完成联盟的临床试验以及伴随的代谢和免疫学研究。相关性：1型糖尿病（T1 D）是由胰岛中产生胰岛素的β细胞的选择性丧失引起的。尽管有许多先进的胰岛素递送系统，但患有TID的受试者继续具有葡萄糖水平的异常波动，导致该疾病的继发性并发症的发展。胰岛移植有可能提供精确和长期的葡萄糖代谢控制，从而预防疾病的继发性并发症。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comment on Harlan. Islet Transplantation for Hypoglycemia Unawareness/Severe Hypoglycemia: Caveat Emptor. Diabetes Care 2016;39:1072-1074.

评论一下哈兰。

DOI：
10.2337/dc16-2691
发表时间：
2017
期刊：
Diabetes care
影响因子：
16.2
作者：
Hering,BernhardJ;Bridges,NancyD;Eggerman,ThomasL;Ricordi,Camillo;ClinicalIsletTransplantationConsortium
通讯作者：
ClinicalIsletTransplantationConsortium

Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic β-cells while repressing α-cell functions.