Glycan-interacting compounds

Abstract

The present invention provides glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include monoclonal antibodies, derivatives and fragments thereof as well as compositions and kits comprising them.

1 . A method of producing a glycan-interacting antibody comprising:
 i. contacting one or more mammals with a composition comprising submaxillary mucin and an adjuvant;   ii. obtaining one or more serum samples from said one or more mammals;   iii. characterizing the binding specificity and/or binding affinity of one or more antibodies present in said one or more serum samples for one or more glycans;   iv. selecting at least one mammal determined to have serum antibodies with desired binding specificity and/or binding affinity for said one or more glycans; and   v. establishing hybridoma cells using spleen cells from said at least one mammal and culturing said hybridoma cells to produce said glycan-interacting antibody.   
     
     
         2 . The method of  claim 1 , wherein characterizing the binding specificity and/or binding affinity of one or more antibodies in said one or more serum samples for one or more glycans is carried out using at least one of an enzyme-linked immunosorbent assay (ELISA) and a glycan array. 
     
     
         3 . The method of  claim 2 , wherein said glycan array comprises at least one glycan selected from Neu5Ac-α-2-6-GalNAc (AcSTn), Neu5Gc-α-2-6-GalNAc (GcSTn), Neu5,9Ac2-α-2,6-GalNAc, Neu9Ac5Gc-α-2,6-GalNAc, and GalNAc (Tn). 
     
     
         4 . The method of  claim 1 , wherein said submaxillary mucin is selected from at least one of porcine submaxillary mucin (PSM), bovine submaxillary mucin (BSM), and ovine submaxillary mucin (OSM). 
     
     
         5 . The method of  claim 1 , wherein said one or more glycans are selected from at least one of AcSTn and GcSTn. 
     
     
         6 . The method of  claim 5 , wherein said desired binding specificity includes binding specificity for AcSTn over GcSTn. 
     
     
         7 . The method of  claim 5 , wherein said desired binding specificity includes binding specificity for both AcSTn and GcSTn. 
     
     
         8 . The method of  claim 1 , wherein said one or more mammals are mice. 
     
     
         9 . The method of  claim 1 , further comprising:
 vi. obtaining the amino acid sequence of at least one variable domain of said glycan-interacting antibody produced by said hybridoma cells and producing at least one recombinant glycan-interacting antibody comprising said amino acid sequence.   
     
     
         10 . The method of  claim 1 , further comprising:
 vi. obtaining the amino acid sequence of at least one complementarity determining region (CDR) of said glycan-interacting antibody produced by said hybridoma cells and producing at least one recombinant glycan-interacting antibody comprising said amino acid sequence.   
     
     
         11 . The method of  claim 10 , wherein said recombinant glycan-interacting antibody comprises a humanized antibody. 
     
     
         12 . An antibody produced by the method of  claim 1 . 
     
     
         13 . The antibody of  claim 12 , wherein said antibody binds AcSTn. 
     
     
         14 . The antibody of  claim 12 , wherein said antibody binds to both AcSTn and GcSTn. 
     
     
         15 . An antibody produced by the method of  claim 10 . 
     
     
         16 . The antibody of  claim 15 , wherein said antibody is humanized. 
     
     
         17 . The antibody of  claim 16 , wherein said antibody binds to AcSTn. 
     
     
         18 . The antibody of  claim 16 , wherein said antibody binds to AcSTn and GcSTn.