Combination therapy of beta-glycolipids and antibodies for the treatment of immune-related disorders

a technology of antibodies and betaglycolipids, applied in the field of conjugation therapy of betaglycolipids and antibodies for the treatment of immune-related disorders, can solve the problems of tissue damage, unexplored role in type 2 diabetes, and inability to fully understand

Inactive Publication Date: 2011-08-18
THE BRIGHAM & WOMEN S HOSPITAL INC +1
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Autoimmunity results from the dysregulation of the immune system leading to tissue damage.
Nature reviews 7:988-994 (2007)] their potential role in type 2 diabetes has not been well explored and is not fully understood [Yeh, S. H. et al.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Combination therapy of beta-glycolipids and antibodies for the treatment of immune-related disorders
  • Combination therapy of beta-glycolipids and antibodies for the treatment of immune-related disorders
  • Combination therapy of beta-glycolipids and antibodies for the treatment of immune-related disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

Significant Synergistic Effect of Orally Administered Combination of Anti-CD3 Antibody and β-Glucosylceramide (GC) on Metabolic Syndrome Model

[0271]In order to investigate the potential effect of combining two different immune-modulatory compounds on an immune-related disorder such as the metabolic syndrome, the ob / ob leptin deficient mice that manifest insulin resistance, hypelipidemia, fatty liver, and diabetes, were used as an animal model.

[0272]Four groups of ob / ob mice were tested, groups 1 and 2 served as control groups (group of untreated mice and group of mice treated with GC and Isotype Control, respectively), group 3 were treated with anti CD3 (5 microgram) antibody and group 4 were orally administered with a combination of anti-CD3 (5 μg) antibody and β-glucosylceramide (GC, 100 μg) per dose for five consecutive days. Animals were assessed on days 10 and 28. The doses studied were based on previous studies of anti-CD3 and GC in animal models [Ochi, H., et al. Nat. Med. 12...

example 2

Oral Combined Composition of Anti-CD3 Plus GC Reduces Hepatic Fat Accumulation and Pancreatic Hyperplasia

[0276]The inventors next investigated the beneficial effect of the combined oral composition of anti-CD3 plus GC treatment of ob / ob mice by pathologic analysis of pancreas, liver and muscle. As shown in FIG. 3, animals fed with the anti-CD3 plus GC combination demonstrated a significant reduction in pancreatic hyperplasia (p<0.005 vs. PBS) and hepatic fat accumulation (p<0.005 vs. PBS). The anti-CD3 plus GC combination was significantly much more effective than anti-CD3 or GC alone, although some effect was observed when the compounds given individually. In addition, a reversal of muscle fiber thinning and increased nuclei was clearly observed in animals treated with the oral combination of anti-CD3 plus GC.

example 3

Oral Combination of Anti-CD3 plus GC Enhances Production of TGF-β and IL-10 in the Mesenteric Lymph Node (MLN)

[0277]To investigate the potential mechanisms by which oral combination of anti-CD3 plus GC affected the metabolic abnormalities describe above, the inventors next measured cytokine production by MLN cells obtained from the different experimental groups, that were then stimulated in vitro with 1 μg / ml anti-CD3 for five days. As shown in FIGS. 4A and 4B, a marked increase in the production of both TGF-β and IL-10, respectively, was found in MLN cells obtained from animals treated with the anti-CD3 plus GC combination (P<0.005 vs. PBS). No effects were observed with anti-CD3 or GC given alone. Oral combination of anti-CD3 plus GC also decreased IL-2 (P<0.005) and IFN-γ secretion (P<0.005) vs. PBS fed animals (FIGS. 4C and 4D, respectively). A similar increase of TGF-β and IL-10 was also observed in splenocytes (not shown). The inventors next measured cytokine levels in superna...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
diameteraaaaaaaaaa
weight percentaaaaaaaaaa
weight percentaaaaaaaaaa
Login to view more

Abstract

The present invention relates to a combination therapy for the treatment of immune-related disorders. More particularly, the invention relates to oral or mucosal synergistic compositions combining beta-glycolipids, preferably, β-glycosphingolipids with immunoglobulin molecules specific for at least one antigen derived from a component of the immune system, specifically an anti-CD3 antibody. The invention further provides methods kits and uses of the combined compositions of the invention for immuno-modulation and thereby for the treatment of immune-related disorders. In a preferred embodiment, anti-CD3 anti-body (OKT3) is orally administered in combination with β-glucosylceramide (also known as glycocerebroside) in an animal model of type 2 diabetes.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a combination therapy for treating immune-related disorders. More particularly, the invention relates to oral or mucosal compositions combining beta-glycolipids, preferably, beta-glycosphingolipids with immunoglobulin molecules, specifically, anti CD3 antibodies. The invention further provides methods, kits using the combined compositions for immuno-modulation and thereby for the treatment of immune-related disorders.BACKGROUND OF THE INVENTION[0002]Throughout this application, various publications are referred to. These publications, and references included therein, are incorporated herein in their entirety.[0003]In many instances, combination therapies employing two or more therapeutic compounds are required to adequately address different medical conditions and / or effects of a certain disorder under treatment. Thus, β-glycolipides which were previously shown by part of the inventors as having an immuno-modulatory effect...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K35/12A61P29/00A61P37/06A61P3/00
CPCA61K31/7032A61K45/06C07K16/2809A61K39/3955A61K31/7028A61K2300/00A61P29/00A61P3/00A61P37/02A61P37/06A61P3/10
Inventor ILAN, YARONWEINER, HOWARD L.
Owner THE BRIGHAM & WOMEN S HOSPITAL INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap