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Immunomodulatory methods using oligosaccharides

a technology of immunomodulatory methods and oligosaccharides, which is applied in the field of immunomodulatory methods using oligosaccharides, can solve the problems of not showing whether human immune cells (e.g., human immune cells in the absence of i>s. mansoni /i>infection) are responsive to lewis antigen-containing compounds, and not showing whether cell types, produce il-, and other cytokines that regulate the development o

Inactive Publication Date: 2006-02-23
HARN DONALD A +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The patent text describes methods for influencing the immune response by modulating the interaction of immune cells with a compound containing a Lewis antigen. This interaction can lead to the production of cytokines that regulate the development of a Th1 or Th2 response, which can be useful in treating a wide range of disorders such as cancer, infectious diseases, allergies, and autoimmune diseases. The methods involve contacting immune cells with a stimulatory or inhibitory form of the compound containing a Lewis antigen. The patent also describes pharmaceutical compositions containing the compound and a carrier for pharmaceutical administration. Overall, the patent provides a way to modulate the immune response and influence the development of a specific response."

Problems solved by technology

This work, however, did not demonstrate whether human immune cells (e.g., human immune cells in the absence of S. mansoni infection) were responsive to Lewis antigen-containing compounds, nor whether cell types other than B cells, such as macrophages or T cells, could produce IL-10 in response to stimulation with compounds comprising a Lewis antigen in the absence of S. mansoni infection.
Moreover, this work did not demonstrate whether production other cytokines that regulate development of Th1 and Th2 responses, such as IL-4, could be stimulated

Method used

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  • Immunomodulatory methods using oligosaccharides
  • Immunomodulatory methods using oligosaccharides
  • Immunomodulatory methods using oligosaccharides

Examples

Experimental program
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Effect test

example 1

[0088] In this example, the ability of macrophages to produce IL-10 upon stimulation with various oligosaccharide conjugates was examined. Granuloma macrophages were prepared from C57BL / 6 mice as described in Flores Villanueva, P.O., et al. (1994) J. Immunol. 153:5190-5199 and Flores Villanueva, P.O., et al. (1994) J. Immunol. 152:1847-1855. Two million cells in 1 ml of DMEM, 10 % FCS were incubated with either no stimulant (i.e., medium alone; a negative control), lipopolysaccharide (LPS; at 20 μg / ml; a positive control), schistosome egg antigen (SEA; at 10 μg / ml), various sugars conjugated to human serum albumin (at 100 μg / ml) or human serum albumin alone (HSA; at 100 μg / ml; a negative control). The sugar conjugates tested were lacto-N-fucopentaose III (LNFP-III), lacto-N-neotetraose (LNT) and Lewisy (Ley). The oligosaccharide conjugates were obtained from Accurate Chemicals, Westbury, N.Y.

[0089] At various time points (24, 48 and 72 hours), the level of IL-10 in the supernatant ...

example 2

[0092] In this example, the ability of peripheral blood mononuclear cells (PBMCs) from humans suffering from various disorders to produce IL-10 upon stimulation with various oligosaccharide conjugates was examined. Human PBMCs were obtained from: 1) an individual who was allergic to pollen; 2) an individual suffering from lung carcinoma and 3) an individual suffering from colon carcinoma. One million PBMC in RPMI-1640 medium containing 10% human AB serum were incubated with either no stimulant (i.e., medium alone; a negative control), lipopolysaccharide (LPS; at 20 μg / ml; a positive control), various sugars conjugated to human serum albumin (at 100 μg / ml) or human serum albumin alone (HSA; at 100 μg / ml; a negative control). The sugar conjugates tested were lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-neotetraose (LNT) and Lewisy (Ley).

[0093] After 24 hours, the level of IL-10 (in pg / ml) in the supernatant was determined by two-site ELISA as describe...

example 3

[0096] In this example, the ability of peripheral blood mononuclear cells (PBMCs) from three humans with B lymphomas to produce IL-10 upon stimulation with various oligosaccharide conjugates was examined. One million PBMC in RPMI-1640 medium containing 10% human AB serum were incubated with either no stimulant (i.e., medium alone; a negative control), lipopolysaccharide (LPS; at 20 μg / ml; a positive control), various sugars conjugated to human serum albumin (at 100 μg / ml) or human serum albumin alone (HSA; at 100 μg / ml; a negative control). The sugar conjugates tested were lacto-N-fucopentaose I (LNFP-I), lacto-N-fucopentaose III (LNFP-III), lacto-N-neotetraose (LNT), Lewisy (Ley) and lacto-N-difucohexose I (LND).

[0097] After 24 hours, the level of IL-10 (in pg / ml) in the supernatant was determined by two-site ELISA as described by in Example 2. Additionally, cellular proliferation was measured by standard 3H-thymidine uptake at 90 hours.

[0098] The results are shown below in Table...

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Abstract

Methods for modulating immune responses are provided. The methods involve contacting an immune cell with an agent that modulates interaction of a compound comprising a Lewis antigen with the immune cell such that production by the immune cell of at least one cytokine that regulates development of a T helper type 1 or T helper type 2 response is modulated. In one embodiment, the agent is a stimulatory form of a compound comprising a Lewis antigen, such as a Lewisy, Lewisx or Lewisa oligosaccharide, or a derivative thereof. In another embodiment, the agent is an inhibitory form of a compound comprising a Lewis antigen, such as a Lewisy, Lewisx or Lewisa oligosaccharide, or a derivative thereof. In various embodiments, the immune cell is a human immune cell, a macrophage or a T cell. Pharmaceutical compositions for modulating immune responses are also provided.

Description

RELATED APPLICATION [0001] This application is a continuation of U.S. application Ser. No. 08 / 597518 filed Jan. 31, 1996 (now U.S. Pat. No. 6841543, issued Jan., 11, 2005), the entire contents of which are hereby incorporated by reference.GOVERNMENT FUNDING [0002] Work described herein was supported under grant AI 27448 awarded by the National Institutes of Health. The U.S. government therefore may have certain rights in this invention.BACKGROUND OF THE INVENTION [0003] The T lymphocyte compartment of the immune system can be divided into a variety of cell subsets. For example, CD4+ T cells represent the T helper cell subset, whereas CD8+ T cells represent the cytotoxic T cell subset. Additionally, CD4+ T helper cells mature into distinct subpopulations that produce different panels of cytokines: the T helper type 1 (Th1) subset produces interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-↑ (TNF-β), whereas the T helper type 2 (Th2) subset produces interleukin-4 (IL...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/739A61K31/00A61K38/00A61K31/704A61K38/38A61K39/00A61K39/39A61P37/00A61P37/08
CPCA61K31/702A61K31/739A61K38/38A61K39/39Y10S530/813A61K2039/57C07H15/00C07K14/5428A61K2039/55511A61P37/00A61P37/08
Inventor HARN, DONALD A.VELUPILLAI, PALANIVEL
Owner HARN DONALD A
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