Procurement of Leukapheresis Products From End Stage Liver Disease (ESLD) Patients for Immunological Studies
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Suppressive Function of Expanded Cells Will be Assessed Using in Vitro Assays of Alloreactivity (Mixed Lymphocyte Culture)
研究概览
简要总结
Regulatory CD4+CD25+ T cells (Treg) derived from the thymus and/or periphery can control immune responsiveness to auto- and allo-antigens. However, there have been few efforts to harness the therapeutic potential of isolated Tregs to control graft rejection and inducing transplantation tolerance in solid organ recipients. In order for Tregs to be used as a clinical treatment, the following properties are necessary: ex vivo generation of sufficient numbers of cells, migration in vivo to sites of antigenic reactivity, ability to suppress rejection in an alloantigen-specific manner, and survival/expansion after infusion. The and others have demonstrated 1) the feasibility of expanding Treg ex vivo, 2) the ability of these cells to down-regulate allogeneic immune responses in vitro, and 3) the efficacy of Treg for prevention of allograft rejection in animal models. In kidney transplant, the investigators have developed strategies for the ex vivo expansion of naturally occurring human Tregs (nTregs) from leukapheresis products that would allow for the clinical employment of this cellular therapy. The investigators are also interested in this approach in patients with end stage liver disease (ESLD) undergoing liver transplantation (LT). Our central hypothesis is that alloreactive human nTreg with suppressive action can be expanded ex vivo from ESLD patients (this proposal) and used to both prevent liver transplant rejection and facilitate the minimization and withdrawal of drug-based immunosuppression (future proposals). This application will further define and validate efficient methods for ex vivo expansion of human CD4+CD25+CD127- FOXP3+nTregs cells in ESLD. The investigators herein propose to use leukapheresis products obtained from patients with ESLD to further refine and optimize protocols for expansion of Tregs. Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture).
详细描述
Regulatory CD4+CD25+ T cells (Treg) derived from the thymus and/or periphery can control immune responsiveness to auto- and allo-antigens. However, there have been few efforts to harness the therapeutic potential of isolated Tregs to control graft rejection and inducing transplantation tolerance in solid organ recipients. In order for Tregs to be used as a clinical treatment, the following properties are necessary: ex vivo generation of sufficient numbers of cells, migration in vivo to sites of antigenic reactivity, ability to suppress rejection in an alloantigen-specific manner, and survival/expansion after infusion. We and others have demonstrated 1) the feasibility of expanding Treg ex vivo, 2) the ability of these cells to down-regulate allogeneic immune responses in vitro, and 3) the efficacy of Treg for prevention of allograft rejection in animal models. In kidney transplant, we have developed strategies for the ex vivo expansion of naturally occurring human Tregs (nTregs) from leukapheresis products that would allow for the clinical employment of this cellular therapy. We are also interested in this approach in patients with end stage liver disease (ESLD) undergoing liver transplantation (LT). Our central hypothesis is that alloreactive human nTreg with suppressive action can be expanded ex vivo from ESLD patients (this proposal) and used to both prevent liver transplant rejection and facilitate the minimization and withdrawal of drug-based immunosuppression (future proposals). This application will further define and validate efficient methods for ex vivo expansion of human CD4+CD25+CD127- FOXP3+nTregs cells in ESLD. We herein propose to use leukapheresis products obtained from patients with ESLD to further refine and optimize protocols for expansion of Tregs. Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •>18 years old,
- •ESLD MELD <25,
- •No recent infection,
- •no hepatic decompensation,
- •no history of HIV,
- •weight > 110 lbs,
- •platelets > 50,000,
- •HGB >10,
- •no prior organ transplant
排除标准
- •Patients ineligible for liver transplant,
- •patients who do not understand why the study procedures are being conducted,
- •subjects who do not meet all inclusion criteria.
研究组 & 干预措施
Leaukapheresis of End Stage Liver Disease Patients
Leukapheresis. All subjects will receive the same treatment arm.
干预措施: Leukapheresis (Procedure)
结局指标
主要结局
Suppressive Function of Expanded Cells Will be Assessed Using in Vitro Assays of Alloreactivity (Mixed Lymphocyte Culture)
时间窗: 21 days
Assay testing - Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture). The in vitro assays will test whether the expanded Tregs will retain their suppressive function.
Number of Regulatory CD4+CD25+ T Cells Obtained From 150 ml of Peripheral Blood in an ESLD Patient
时间窗: 21 days
Number of regulatory CD4+CD25+ T cells after 21 days in culture from leukapheresis product (150 ml of processed blood) from ESLD patient.
次要结局
未报告次要终点
研究者
Josh Levitsky
Associate Professor of Medicine
Northwestern University