Stimulation of an immune response with antibodies labeled with the alpha-galactosyl epitope

Abstract

Humoral and cellular immune responses against tumor cells and infectious agents are induced in a mammal using an antibody that binds with an epitope of an antigen that is associated with a tumor or an infectious agent, and that contains at least one α-galactosyl epitope. Such an antibody is capable of forming a complex with cells that express the target epitope and with antibodies that bind α-galactosyl epitopes. Suitable antibodies include molecules that contain at least one engineered glycosylation site in the constant region of the heavy chain.

What is claimed is:  
     
         1 . A method for stimulating humoral and cellular immune responses in a mammal against a tumor that expresses a tumor associated antigen (TAA) or against a disease caused by an infectious agent, said method comprising the step of: 
 (a) administering an α-Gal antibody to the mammal, wherein said α-Gal antibody comprises: 
 (i) an antibody component that binds with a specified target epitope, wherein said target epitope is an epitope of a TAA or an epitope of an antigen associated with an infectious agent, and  
 (ii) at least one α-galactosyl epitope,  
   wherein said α-Gal antibody can form a complex with cells that express said target epitope and antibodies that bind said α-galactosyl epitope.    
     
     
         2 . The method of  claim 1 , wherein said antibody component is selected from the group consisting of: 
 (a) a murine monoclonal antibody;    (b) a humanized antibody derived from a murine monoclonal antibody;    (c) a human monoclonal antibody; and    (d) an antibody fragment derived from (a), (b) or (c).    
     
     
         3 . The method of  claim 2 , wherein said antibody fragment is selected from the group consisting of F(ab′) 2 , F(ab) 2 , Fab′ and Fab.  
     
     
         4 . The method of  claim 1 , wherein said antibody component comprises at least one α-galactosyl epitope that is sialylated.  
     
     
         5 . The method of  claim 1 , wherein said method further comprises the step of administering an oligosaccharide prior to or during step (a), wherein said oligosaccharide specifically binds with antibodies that bind the α-galactosyl epitope.  
     
     
         6 . The method of  claim 1 , wherein said method further comprises the step of administering an oligosaccharide prior to and during step (a), wherein said oligosaccharide specifically binds with antibodies that bind the α-galactosyl epitope.  
     
     
         7 . A mutated antibody comprising: 
 (a) a heavy chain having a constant region with an engineered glycosylation site, and    (b) a carbohydrate moiety attached to said engineered glycosylation site, wherein said carbohydrate moiety comprises at least one α-galactosyl epitope.    
     
     
         8 . The mutated antibody of  claim 7 , wherein said heavy chain comprises a human IgG1 CH1 domain, and wherein said CH1 domain contains said engineered glycosylation site.  
     
     
         9 . The mutated antibody of  claim 8 , wherein said carbohydrate moiety is attached at about amino acid 162 of said CH1 domain, according to Kabat's numbering system.  
     
     
         10 . The mutated antibody of  claim 8 , wherein said carbohydrate moiety is attached at about amino acid 198 of said CH1 domain, according to Kabat's numbering system.  
     
     
         11 . The mutated antibody of  claim 7 , wherein said mutated antibody further comprises a variable region that binds an epitope of a tumor associated antigen or an epitope of an antigen associated with an infectious agent.  
     
     
         12 . A chimeric mLL2 antibody comprising: 
 (a) a light chain variable region with a glycosylation site, and    (b) a carbohydrate moiety attached to said engineered glycosylation site, wherein said carbohydrate moiety comprises at least one α-galactosyl epitope.    
     
     
         13 . The chimeric mLL2 antibody of  claim 12 , wherein said glycosylation site is located in the framework-1 sequence of the kappa light chain variable region.