Immunomodulatory methods using oligosaccharides

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 Lewis y , Lewis x or Lewis a oligosaccharide, or a derivative thereof. In another embodiment, the agent is an inhibitory form of a compound comprising a Lewis antigen, such as a Lewis y , Lewis x or Lewis a 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.

1 . An immunomodulatory method comprising contacting a human immune cell with an agent that modulates interaction of a compound comprising a Lewis antigen with the human immune cell such that production by the human immune cell of at least one cytokine that regulates development of a T helper type 1 (Th1 ) or T helper type 2 (Th2) response is modulated.  
   
   
       2 . The method of  claim 1 , wherein production of IL-10 by the human immune cell is stimulated.  
   
   
       3 . (canceled)  
   
   
       4 . The method of  claim 1 , wherein the agent comprises a Lewis y  oligosaccharide or a derivative thereof; a Lewis x  oligosaccharide or a derivative thereof; a Lewis a  oligosaccharide or a derivative thereof; or a Lewis b  oligosaccharide or a derivative thereof.  
   
   
       5 - 6 . (canceled)  
   
   
       7 . The method of  claim 1 , wherein the agent is administered to a human subject such that production by human immune cells of the human subject of at least one cytokine that regulates development of a Th1 or Th2 response is stimulated.  
   
   
       8 . The method of  claim 1 , wherein production of IL-10 by the human immune cell is inhibited.  
   
   
       9 - 12 . (canceled)  
   
   
       13 . The method of  claim 1 , wherein the agent is administered to a human subject such that production by human immune cells of the human subject of at least one cytokine that regulates development of a Th1 or Th2 response is inhibited.  
   
   
       14 . The method of  claim 1 , wherein the human immune cell is a T cell.  
   
   
       15 . The method of  claim 1 , wherein the human immune cell is a macrophage.  
   
   
       16 . The method of  claim 1 , wherein the human immune cell is a B cell.  
   
   
       17 - 22 . (canceled)  
   
   
       23 . The method of  claim 15 , wherein the agent is administered to a subject such that production by macrophages of the subject of at least one cytokine that regulates development of a Th1 or Th2 response is stimulated.  
   
   
       24 - 28 . (canceled)  
   
   
       29 . The method of  claim 15 , wherein the agent is administered to a subject such that production by macrophages of the subject of at least one cytokine that regulates development of a Th1 or Th2 response is inhibited.  
   
   
       30 - 35 . (canceled)  
   
   
       36 . The method of  claim 14 , wherein the agent is administered to a subject such that production by T cells of the subject of at least one cytokine that regulates development of a Th1 or Th2 response is stimulated.  
   
   
       37 - 41 . (canceled)  
   
   
       42 . The method of  claim 14 , wherein the agent is administered to a subject such that production by T cells of the subject of at least one cytokine that regulates development of a Th1 or Th2 response is inhibited.  
   
   
       43 . A pharmaceutical composition comprising an agent that modulates interaction of a compound comprising a Lewis antigen with human immune cells of a human subject in an amount sufficient to modulate production by the human immune cells of at least one cytokine that regulates development of a T helper type 1 (Th1) or a T helper type 2 (Th2) response when the agent is administered to the human subject, and a pharmaceutically acceptable carrier.  
   
   
       44 . The pharmaceutical composition of  claim 43 , wherein the agent is a stimulatory form of a compound comprising a Lewis antigen.  
   
   
       45 . The pharmaceutical composition of  claim 44 , wherein the Lewis antigen comprises a Lewis y  oligosaccharide or a derivative thereof; a Lewis x  oligosaccharide or a derivative thereof; a Lewis a  oligosaccharide or a derivative thereof or a Lewis b  oligosaccharide or a derivative thereof.  
   
   
       46 - 47 . (canceled)  
   
   
       48 . The pharmaceutical composition of  claim 43 , wherein the agent is an inhibitory form of a compound comprising a Lewis antigen.  
   
   
       49 . The pharmaceutical composition of  claim 48 , wherein the Lewis antigen comprises a Lewis y  oligosaccharide or a derivative thereof; a Lewis x  oligosaccharide or a derivative thereof; a Lewis a  oligosaccharide or a derivative thereof; or a Lewis b  oligosaccharide or a derivative thereof.  
   
   
       50 - 54 . (canceled)  
   
   
       55 . A pharmaceutical composition comprising a conjugate of a Lewis antigen, or derivative thereof, and a carrier molecule, such that the Lewis antigen, or derivative thereof, comprises 10-25% of the conjugate by weight, in an amount sufficient to stimulate production of at least one cytokine that regulates development of a T helper type 1 (Th1) or a T helper type 2 (Th2) response when the agent is administered to the subject, and a pharmaceutically acceptable carrier.