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Compositions and methods for the prevention and treatment of autoimmune conditions

a technology for autoimmune conditions and compositions, applied in the field of immunology and medicine, can solve problems such as the difficulty of treating patients with peptides

Inactive Publication Date: 2011-03-10
THE GENERAL HOSPITAL CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a new way to treat autoimmune diseases like type 1 diabetes (T1D) and multiple sclerosis (MS). The method involves using particles that have been designed to expand specific T cells and eliminate others. These particles contain a peptide and a molecule called MHC, which helps to control the immune system. By selectively expanding these T cells and deleting the ones that cause the disease, the treatment can prevent and ameliorate the symptoms of T1D without causing generalized immunosuppression. The patent also describes the use of tolerogenic particles, which can help to restore normal immune function. Overall, this new approach offers a promising way to treat autoimmune diseases and prevent them from coming back.

Problems solved by technology

It would be difficult to treat a patient with peptides because, as is the case of IGRP, this would require several milligrams of peptides per dose.

Method used

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  • Compositions and methods for the prevention and treatment of autoimmune conditions
  • Compositions and methods for the prevention and treatment of autoimmune conditions
  • Compositions and methods for the prevention and treatment of autoimmune conditions

Examples

Experimental program
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Effect test

example 1

T1D Protection by Treatment with Peptide / MHC-Coated Nanoparticles

[0176]Diabetes protection by treatment with super-paramagnetic nanoparticles coated with NRP-V7 / Kd monomers. To study whether NRP-V7 / Kd-coated nanoparticles are tolerogenic in vivo, 8.3-TCR-transgenic NOD mice were treated (also referred to as 8.3-NOD or Vα17.4+ TCR-TG mice further below) with several i.v. injections of a small volume of particles (5 μl, carrying 0.6 μg of NRP-V7, once every 3 days). The transgenic high-avidity IGRP206-214-reactive splenic CD8+ T-cell pools of these mice were significantly depleted in three doses (the splenic CD8:CD4 ratios dropped from ˜4 to ˜1) (FIG. 1A). The few non-deleted CD8+ T-cells showed signs of prior activation as determined by assessing CD44 expression (FIG. 1B) and were hyporesponsive to antigenic stimulation in vitro, suggesting that they had been anergized by the treatment (FIG. 1C).

[0177]To study the effectiveness of ‘multiplexing’, paramagnetic beads (referred herein t...

example 2

Testing the Ability of Iron Oxide Nanoparticles Coated with Human Type 1 Diabetes-Relevant Peptide / HLA Complexes to Restore Normoglycemia

[0200]“Humanized” mice expressing HLA transgenes and peptide / HLA complexes available for the proposed studies. As mentioned above, peptides derived from insulin and IGRP are primary targets of CD8+ T cells in wild-type NOD mice. Assessment of human MHC molecules (Human Leukocyte Antigens, HLA) presented peptides derived from these two autoantigens during diabetogenesis is being investigated in ‘humanized’ HLA-transgenic NOD mice. Studies focused initially on HLAA*0201, a MHC molecule that is expressed by nearly 50% of certain ethnic groups. This study employs the strain designated NOD.β2mnull.HHD, which lacks the murine β2 macroglobulin gene and expresses the chimeric monochain construct HHD (Pascolo et al., 1997). This construct encodes human β2m covalently linked to the α1 and α2 domains of human HLA-A*0201, and the α3, transmembrane, and cytop...

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Abstract

The methods include selectively reducing or expanding T cells according to the antigenic specificity of the T cells. Therefore, the present invention can be used to reduce or eliminate pathogenic T cells that recognize autoantigens, such as beta cell specific T cells. As such, the present invention can be used to prevent, treat or ameliorate autoimmune diseases such as IDDM. Furthermore, the present invention can be used to expand desirable T cells, such as anti-pathogenic T cells to prevent, treat and / or ameliorate autoimmune diseases.

Description

[0001]This application claims priority to U.S. Provisional Patent application No. 60 / 893,530 filed on Mar. 7, 2007, which is hereby incorporated by reference in its entirety.[0002]The United States Government owns rights in the present invention pursuant to grant 5R01 DK064850-03 from the NIH.BACKGROUND OF THE INVENTION[0003]I. Field of the Invention[0004]This invention embodies compositions and methods related to immunology and medicine. In particular the invention is related to diagnostics and therapeutics for the diagnosis and treatment of autoimmune conditions, particularly diabetes.[0005]II. Background[0006]Antigen vaccination can be used for the induction of T-cell tolerance in autoimmunity. Administration of autoantigenic proteins or peptides in solution can blunt the initiation and / or progression of autoimmunity in experimental models of autoimmune disease (Wraith et al., 1989; Metzler and Wraith, 1993; Liu and Wraith, 1995; Anderton and Wraith, 1998; Karin et al., 1994). Ho...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/385C07K17/00
CPCA61K39/0008A61K39/385A61K47/48861A61K47/48884A61K2039/55555G01N2800/042G01N33/54313G01N33/564G01N33/56972G01N2333/70539A61K2039/605A61K47/6923A61K47/6929A61P1/02A61P1/04A61P1/16A61P11/06A61P15/08A61P17/00A61P17/02A61P17/12A61P17/14A61P19/02A61P21/00A61P25/00A61P25/28A61P29/00A61P3/10A61P37/00A61P37/02A61P37/06A61P37/08A61P5/00A61P5/14A61P5/18A61P7/06A61P9/04A61K9/5094A61K2039/572A61K2039/60A61K2039/6093A61K2039/627
Inventor SANTAMARIA, PEDROMOORE, ANNA
Owner THE GENERAL HOSPITAL CORP
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