Active tolerosomes, a novel therapy for type 1 diabetes

活性耐受体,一种治疗 1 型糖尿病的新疗法

基本信息

  • 批准号:
    6925814
  • 负责人:
  • 金额:
    $ 15.4万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-04-01 至 2007-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Type 1 diabetes mellitus and its associated complications are a major health problem in the US. The disease, which originates from a breakdown in T-cell tolerance, has a significant pre-diabetic stage, during which effected individuals are essentially asymptomatic. This provides a window of opportunity for therapeutic intervention. Our aim is to generate an immune-based therapy that will selectively target the pathogenic cells without causing a global disturbance of the immune system. Productive interactions between T-cells and their targets are typically characterized by the formation of an "immune synapse" containing combinations of both clonotypic and oligotypic receptor-ligand pairs. Our central hypothesis is that antigen-specific therapy will require reagents which can mimic these events. As part of normal homeostatic mechanisms, T-cells stimulated through their antigen receptors can undergo activation induced apoptosis. This preferentially occurs to the potentially diabetogenic Th1 population, and is believed to be defective in at least some diabetic individuals due to a failure to induce pro-apoptotic molecules to sufficient levels. We will create synthetic antigen-specific pro-apoptotic molecules predicted to restore this functional deficit in vivo. These novel reagents should induce apoptosis of the targeted (pathogenic) cells, but spare potentially protective ones, and may therefore lead to a change in the immune balance, and tolerance. We will test this hypothesis using established model systems. The project will involve three phases. 1. The creation of single chain peptide-MHC class II complexes and chimeras with Fas ligand by molecular cloning techniques. 2. In vitro analysis of the reagents using a panel of antigen-specific T-cell clones, and primary cells isolated from transgenic, pre-diabetic or newly diabetic NOD mice. 3. Analysis of the reagents in vivo following adoptive transfer of diabetogenic cells into NOD/SCI mouse models of diabetes. Ultimately we envisage that this novel strategy will form the basis for improved therapies for pre-diabetic or newly diabetic human subjects.
描述(由申请人提供):1型糖尿病及其相关并发症是美国的主要健康问题。该疾病起源于T细胞耐受性的破坏,具有显著的糖尿病前期,在此期间受影响的个体基本上无症状。这为治疗干预提供了机会之窗。我们的目标是产生一种基于免疫的疗法,该疗法将选择性地靶向致病细胞,而不会引起免疫系统的整体干扰。 T细胞与其靶之间的有效相互作用的特征通常在于形成含有克隆型和寡型受体-配体对的组合的“免疫突触”。我们的中心假设是,抗原特异性治疗将需要能够模拟这些事件的试剂。作为正常稳态机制的一部分,通过其抗原受体刺激的T细胞可以经历活化诱导的细胞凋亡。这优先发生在潜在的致糖尿病性Th 1群体中,并且被认为在至少一些糖尿病个体中是有缺陷的,这是由于未能将促凋亡分子诱导到足够的水平。我们将创造合成的抗原特异性促凋亡分子,预测在体内恢复这种功能缺陷。这些新型试剂应诱导靶向(致病)细胞的凋亡,但保留潜在的保护性细胞,因此可能导致免疫平衡和耐受性的变化。我们将使用已建立的模型系统来检验这一假设。该项目将分三个阶段进行。 1.利用分子克隆技术制备单链肽-MHC Ⅱ类复合物和Fas配体嵌合体。 2.使用一组抗原特异性T细胞克隆和从转基因、糖尿病前期或新糖尿病NOD小鼠分离的原代细胞进行试剂的体外分析。 3.在将致糖尿病细胞过继转移到糖尿病的NOD/SCI小鼠模型中后,体内分析试剂。 最终,我们设想,这种新的策略将形成糖尿病前期或新糖尿病人类受试者的改进疗法的基础。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

HOWARD W DAVIDSON其他文献

HOWARD W DAVIDSON的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('HOWARD W DAVIDSON', 18)}}的其他基金

Multimodal analysis of the "honeymoon period" in autoimmune diabetes
自身免疫性糖尿病“蜜月期”的多模态分析
  • 批准号:
    10595074
  • 财政年份:
    2022
  • 资助金额:
    $ 15.4万
  • 项目类别:
Multimodal analysis of the "honeymoon period" in autoimmune diabetes
自身免疫性糖尿病“蜜月期”的多模态分析
  • 批准号:
    10443339
  • 财政年份:
    2022
  • 资助金额:
    $ 15.4万
  • 项目类别:
Analysis of diabetogenic human T cell receptors
致糖尿病的人类 T 细胞受体分析
  • 批准号:
    8311935
  • 财政年份:
    2011
  • 资助金额:
    $ 15.4万
  • 项目类别:
Development of novel diabetes autoantibody assays based on luciferase reporters
基于荧光素酶报告基因的新型糖尿病自身抗体测定的开发
  • 批准号:
    7962864
  • 财政年份:
    2010
  • 资助金额:
    $ 15.4万
  • 项目类别:
Development of novel diabetes autoantibody assays based on luciferase reporters
基于荧光素酶报告基因的新型糖尿病自身抗体测定的开发
  • 批准号:
    8075000
  • 财政年份:
    2010
  • 资助金额:
    $ 15.4万
  • 项目类别:
Active tolerosomes, a novel therapy for type 1 diabetes
活性耐受体,一种治疗 1 型糖尿病的新疗法
  • 批准号:
    7027696
  • 财政年份:
    2005
  • 资助金额:
    $ 15.4万
  • 项目类别:
Cloning of molecular targets of CMI in type 1 diabetes
1型糖尿病CMI分子靶点的克隆
  • 批准号:
    8038522
  • 财政年份:
    1996
  • 资助金额:
    $ 15.4万
  • 项目类别:
Cloning of molecular targets of Cell Mediated Autoimmunity in Type 1 Diabetes
1 型糖尿病细胞介导的自身免疫分子靶标的克隆
  • 批准号:
    8636443
  • 财政年份:
    1996
  • 资助金额:
    $ 15.4万
  • 项目类别:
Cloning of molecular targets of Cell Mediated Autoimmunity in Type 1 Diabetes
1 型糖尿病细胞介导的自身免疫分子靶标的克隆
  • 批准号:
    8448325
  • 财政年份:
    1996
  • 资助金额:
    $ 15.4万
  • 项目类别:
Cloning of molecular targets of Cell Mediated Autoimmunity in Type 1 Diabetes
1 型糖尿病细胞介导的自身免疫分子靶标的克隆
  • 批准号:
    8039796
  • 财政年份:
    1996
  • 资助金额:
    $ 15.4万
  • 项目类别:

相似海外基金

Effect of tofacitinib on skin initiated autoimmunity in the NOD mouse
托法替布对 NOD 小鼠皮肤引发的自身免疫的影响
  • 批准号:
    324045
  • 财政年份:
    2015
  • 资助金额:
    $ 15.4万
  • 项目类别:
    Studentship Programs
The mechanism of axonal degeneration caused by demyelination in B7-2 KO NOD mouse
B7-2 KO NOD小鼠脱髓鞘导致轴突变性的机制
  • 批准号:
    26461292
  • 财政年份:
    2014
  • 资助金额:
    $ 15.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of slowly progressive type 1 diabetes animal models using the CD28 knock-out NOD mouse
使用 CD28 敲除 NOD 小鼠开发缓慢进展的 1 型糖尿病动物模型
  • 批准号:
    24591319
  • 财政年份:
    2012
  • 资助金额:
    $ 15.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Effect of diet & commensal bacteria on diabetes outcome in NOD mouse
饮食的影响
  • 批准号:
    7941018
  • 财政年份:
    2009
  • 资助金额:
    $ 15.4万
  • 项目类别:
Effect of diet & commensal bacteria on diabetes outcome in NOD mouse
饮食的影响
  • 批准号:
    7824956
  • 财政年份:
    2009
  • 资助金额:
    $ 15.4万
  • 项目类别:
Effect of Ag-specific CD8+ T cell deletion on diabetogenesis in the NOD mouse
Ag 特异性 CD8 T 细胞缺失对 NOD 小鼠糖尿病发生的影响
  • 批准号:
    7813865
  • 财政年份:
    2008
  • 资助金额:
    $ 15.4万
  • 项目类别:
Effect of Ag-specific CD8+ T cell deletion on diabetogenesis in the NOD mouse
Ag 特异性 CD8 T 细胞缺失对 NOD 小鼠糖尿病发生的影响
  • 批准号:
    8066587
  • 财政年份:
    2008
  • 资助金额:
    $ 15.4万
  • 项目类别:
Effect of Ag-specific CD8+ T cell deletion on diabetogenesis in the NOD mouse
Ag 特异性 CD8 T 细胞缺失对 NOD 小鼠糖尿病发生的影响
  • 批准号:
    7471656
  • 财政年份:
    2008
  • 资助金额:
    $ 15.4万
  • 项目类别:
Effect of Ag-specific CD8+ T cell deletion on diabetogenesis in the NOD mouse
Ag 特异性 CD8 T 细胞缺失对 NOD 小鼠糖尿病发生的影响
  • 批准号:
    7809134
  • 财政年份:
    2008
  • 资助金额:
    $ 15.4万
  • 项目类别:
Effect of Ag-specific CD8+ T cell deletion on diabetogenesis in the NOD mouse
Ag 特异性 CD8 T 细胞缺失对 NOD 小鼠糖尿病发生的影响
  • 批准号:
    7585202
  • 财政年份:
    2008
  • 资助金额:
    $ 15.4万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了