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Peptides for use in treatment and diagnosis of type 1 diabetes

一种组合物、氨基酸的技术，应用在疾病诊断、肽、肽源等方向，能够解决T1D无法治愈等问题

Inactive Publication Date: 2018-01-02
IMMUSANT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is currently no cure for T1D, and T1D management requires lifelong insulin use

Method used

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  • Peptides for use in treatment and diagnosis of type 1 diabetes
  • Peptides for use in treatment and diagnosis of type 1 diabetes
  • Peptides for use in treatment and diagnosis of type 1 diabetes

Examples

Experimental program
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Effect test

example 1

[0185] Example 1. Islet autoimmunity in T1D

[0186] The aim of the study was to quantify and compare T cell responses to islet autoantigens, immunodominant gluten peptides, and pathogen-derived recall antigens before and after oral gluten challenge in patients with both type 1 diabetes (T1D) and celiac disease answer.

[0187] background

[0188] Dietary gluten may play a role in inducing or enhancing islet autoimmunity, but the mechanism remains unclear. In patient-based studies over the past 14 years, short-term "gluten challenges" have provided detailed insight into the immune response in celiac disease. In this study, gluten challenge was first used to study patients affected by celiac disease as well as T1D to detect CD4+ T cells specific for self-antigens implicated in T1D and to test whether islet autoimmunity is affected by gluten immunity effect on reactivation.

[0189] In celiac disease, the most prevalent genetic association is with the MHC class II allele e...

example 21

[0279] Example 2. Gluten immunity and islet autoimmunity in type 1 diabetes

[0280] The aim of this study was to quantify and compare T cell responses to islet autoantigens, immunodominant gluten peptides, and pathogen-derived recall antigens before and after oral gluten challenge in patients with both type 1 diabetes (T1D) and celiac disease answer. CD4+ and CD8+ T cell depletion of whole blood samples is performed in order to determine the specific cell populations of T cell cytokine responses to the T1D peptide antigen being analyzed.

[0281] Human CD4+ and CD8+ T cells were depleted directly from whole blood according to the manufacturer's protocol using CD4 and CD8 Dynabeads, respectively (Dynabeads Human CD4, Life Technologies, #11145D; Dynabeads Human CD8, Life Technologies, #11145D) . Briefly, Dynabeads were resuspended and the required volume was transferred to a 15Ml tube. The volume of beads added to whole blood is calculated as 2x 10 per M1 of whole blood 6...

example 3

[0310] Example 3. Fine mapping of preproinsulin epitopes

[0311] The leader sequence of the preproinsulin epitope was finely mapped with lysine substituted peptides and C- and N-terminal truncations. Figures 1A-1C Diagram showing the dominant 11-mer epitope in preproinsulin p10-20: LLALLALWGPD (SEQ ID NO: 14). In 4 subjects with T1D, the length and observed biological activity in the whole blood IP-10 release assay was compatible with the epitope of CD4 T cells. However, the activity of the 9-mer p8-16:LPLLALLAL (SEQ ID NO: 76) indicated that this is a CD8 T cell epitope and overlaps with the CD4 epitope. Without wishing to be bound by any theory, therapeutic and / or diagnostic peptides according to the present disclosure may be chosen to avoid CD8 activity, but ensure targeting of CD4 T cells. Data are mean values ​​of whole blood IP-10 release from 4 subjects, measured as fold change relative to medium alone (no peptide).

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Abstract

Provided herein are compositions and methods for treating autoimmune diabetes such as type 1 diabetes (T1D), diagnosing autoimmune diabetes such as T1D, assessing treatment efficacy, and selecting subjects for treatment, e.g., using a peptide or epitope disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 082,823, filed November 21, 2014, the contents of which are incorporated herein by reference in their entirety. Background technique [0003] Type 1 diabetes (TlD) is a form of diabetes that results from the destruction of insulin-producing beta cells in the pancreas due to an autoimmune response to the beta cells. About 350 million people worldwide have diabetes, and about 5%-10% of them have T1D. There is currently no cure for T1D, and T1D management requires lifelong insulin use. Contents of the invention [0004] The present disclosure relates to compositions and methods for treating a subject with an autoimmune diabetes such as T1D, evaluating the efficacy of treatment, diagnosing an autoimmune diabetes such as T1D, and selecting a subject for treatment. As described herein, peptides were identified as inducing T c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47C07K14/62C12Q1/02G01N33/68A61K38/17A61K38/28A61P3/10
CPCC07K14/62G01N33/505G01N33/68C07K14/4747A61P3/10A61K39/00C07K16/24C07K16/246C07K16/249G01N33/5088G01N33/5091G01N33/6863G01N33/6866G01N33/6869G01N2333/522G01N2333/54G01N2333/57G01N2800/042G01N2800/52
Inventor 罗伯特·P·安德森
Owner IMMUSANT
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