Adoptive Cellular Gene Therapy in Type 1 Diabetes (T1D)
1 型糖尿病 (T1D) 的过继细胞基因疗法
基本信息
- 批准号:6947201
- 负责人:
- 金额:$ 39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-09-30 至 2007-08-31
- 项目状态:已结题
- 来源:
- 关键词:CD3 moleculeNOD mouseantiantibodyautologous transplantationbiomarkerbiotechnologybone marrow transplantationdendritic cellsdiabetes mellitus therapygene therapyimmunotherapyinflammationinsulin dependent diabetes mellitusinterleukin 4microarray technologyprediabetic statetransfectiontransfection /expression vector
项目摘要
DESCRIPTION (provided by applicant):
Published studies from Dr. Fathman's laboratory have demonstrated that murine T cell hybridomas, retrovirally transduced to express immunoregulatory proteins, can halt the induction or progression of disease in several mouse models of autoimmune disease including collagen-induced arthritis (CIA), experimental allergic encephalomyelitis (EAE) and, in more recent unpublished observations, block the progression from recent onset hyperglycemia to overt type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. These recent unexpected findings offer the potential to intervene in human T1D at the stage of recent onset hyperglycemia with a form of "adoptive cellular gene therapy" that may potentially be extended to the prevention of progression from insulitis to hyperglycemia, not only in the NOD mouse, but in "high risk" pre-diabetic human T1D. The technology required to move from islet-antigen-reactive murine T cell hybridomas, as vehicles for "drug delivery," to murine autologous dendritic cells for gene therapy of T1D, is requested as part of this R21 development and feasibility approach to the treatment of recent onset hyperglycemia in T1D. Preliminary data, obtained recently, support the hypothesis that dendritic cells (DCs) are as effective as T cell hybridomas in delivering the therapeutic regulatory protein(s) to the inflammatory lesions of autoimmunity. A second major goal of the proposed R21 studies (that will continue into the R33 funding) is to use cDNA microarray technology to attempt to understand the mechanism(s) of this form of therapy, as well as potentially identify surrogate markers of success or identify additional targets for therapeutic intervention. It is additionally proposed to use herpes simplex virus type 1 thymidine kinase (HSV1-tk) as a marker to follow the trafficking of adoptively transferred DCs in real time in vivo in NOD mice (R21) and to use this knowledge to transfer the imaging technology to man (R33). Finally, under requested R33 support, a Phase I trial of transduction and infusion of autologous DCs into recently hyperglycemic T1D patients for safety studies and to observe cell trafficking is proposed.
描述(由申请人提供):
Fathman博士实验室发表的研究表明,逆转录病毒转导表达免疫调节蛋白的鼠T细胞杂交瘤可以阻止几种自身免疫性疾病小鼠模型中疾病的诱导或进展,包括胶原诱导的关节炎(CIA),实验性过敏性脑脊髓炎(EAE),以及最近未发表的观察结果,在非肥胖糖尿病(NOD)小鼠中阻断从新近发作的高血糖症到明显的1型糖尿病(T1 D)的进展。这些最近的意外发现提供了在近期发作的高血糖阶段用“过继细胞基因疗法”的形式干预人类T1 D的可能性,所述“过继细胞基因疗法”可能潜在地扩展到预防从胰岛炎进展到高血糖,不仅在NOD小鼠中,而且在“高风险”糖尿病前期人类T1 D中。从胰岛抗原反应性鼠T细胞杂交瘤(作为“药物递送”的载体)到用于T1 D基因治疗的鼠自体树突状细胞所需的技术,被要求作为R21开发和可行性方法的一部分,用于治疗T1 D中近期发作的高血糖症。最近获得的初步数据支持这样的假设,即树突状细胞(DC)在将治疗性调节蛋白递送至自身免疫的炎性病变方面与T细胞杂交瘤一样有效。拟议的R21研究的第二个主要目标(将继续到R33资助)是使用cDNA微阵列技术来尝试了解这种形式的治疗机制,以及潜在地识别成功的替代标记或识别治疗干预的其他靶点。另外提出使用单纯疱疹病毒1型胸苷激酶(HSV 1-tk)作为标记物以在NOD小鼠中体内真实的时间跟踪过继转移的DC的运输(R21),并使用该知识将成像技术转移到人(R33)。最后,在要求的R33支持下,提出了将自体DC转导和输注到最近的高血糖T1 D患者中用于安全性研究和观察细胞运输的I期试验。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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CHARLES GARRISON FATHMAN其他文献
CHARLES GARRISON FATHMAN的其他文献
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{{ truncateString('CHARLES GARRISON FATHMAN', 18)}}的其他基金
Whole blood gene expression to identify biomarkers of disease risk, progression and response to therapy in Type 1 diabetes
全血基因表达可识别 1 型糖尿病疾病风险、进展和治疗反应的生物标志物
- 批准号:
9918349 - 财政年份:2018
- 资助金额:
$ 39万 - 项目类别:
Deaf1 isoforms control changes in PTA expression in the NOD PLN during T1D pathog
Deaf1亚型控制T1D病理过程中NOD PLN中PTA表达的变化
- 批准号:
8097962 - 财政年份:2010
- 资助金额:
$ 39万 - 项目类别:
Deaf1 isoforms control changes in PTA expression in the NOD PLN during T1D pathog
Deaf1亚型控制T1D病理过程中NOD PLN中PTA表达的变化
- 批准号:
8485528 - 财政年份:2010
- 资助金额:
$ 39万 - 项目类别:
Deaf1 isoforms control changes in PTA expression in the NOD PLN during T1D pathog
Deaf1亚型控制T1D病理过程中NOD PLN中PTA表达的变化
- 批准号:
8287113 - 财政年份:2010
- 资助金额:
$ 39万 - 项目类别:
Deaf1 isoforms control changes in PTA expression in the NOD PLN during T1D pathog
Deaf1亚型控制T1D病理过程中NOD PLN中PTA表达的变化
- 批准号:
7887644 - 财政年份:2010
- 资助金额:
$ 39万 - 项目类别:
Autoimmunity Center of Excellence (ACE) at Stanford
斯坦福大学自身免疫卓越中心 (ACE)
- 批准号:
8461899 - 财政年份:2009
- 资助金额:
$ 39万 - 项目类别:
Autoimmunity Center of Excellence (ACE) at Stanford
斯坦福大学自身免疫卓越中心 (ACE)
- 批准号:
7846553 - 财政年份:2009
- 资助金额:
$ 39万 - 项目类别:
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