Carbohydrate structures and uses thereof

Abstract

The present invention provides methods and compositions related to multivalent carbohydrate antigen structures comprising cancer or infection associated ganglioside carbohydrate antigens. Said carbohydrate structures may be used to induce immunity against said carbohydrate antigens. In some embodiments, carbohydrate structures may be administered to a subject thereby inducing immunity in the subject, for example, the administration of a vaccine comprising said carbohydrate structure. Also provided are methods to induce an immune response in a subject in need thereof by administering said carbohydrate structure. Further provided are methods of producing an antibody or TCR that bind said carbohydrate antigens.

1 - 55 . (canceled) 
     
     
         56 . A method of producing an antibody to a carbohydrate antigen, the method comprising
 (a) immunizing a mammal, except for a human, with a composition comprising a carbohydrate structure; and   (b) isolating an antibody that binds to the carbohydrate structure from the mammal or from a hybridoma made using a cell from the mammal,   wherein the carbohydrate structure has the formula
   [(A)-(P) y -(L) z]x -M 
   wherein   A is a carbohydrate antigen, or any portion thereof;   P is a ring, wherein P is not C6-C10 aryl;   y is 0 or 1;   L is a linker;   z is 0 or 1;   x is an integer from 1 to 32;   M is a core, wherein M is not keyhole limpet hemocyanin (KLH).   
     
     
         57 . A method for producing a nucleic acid encoding an antibody to a carbohydrate antigen, the method comprising
 (a) immunizing a mammal, except for a human, with a composition comprising a carbohydrate structure; and   (b) isolating a cell from the mammal of step (a) that expresses an antibody to the carbohydrate antigen; and   (c) isolating a nucleic acid from the cell of step (b) that encodes the antibody to the carbohydrate antigen   wherein the carbohydrate structure has the formula
   [(A)-(P) y -(L) z]x -M 
   wherein   A is a carbohydrate antigen, or any portion thereof;   P is a ring, wherein P is not C6-C10 aryl;   y is 0 or 1;   L is a linker;   z is 0 or 1;   x is an integer from 1 to 32;   M is a core, wherein M is not keyhole limpet hemocyanin (KLH).   
     
     
         58 . The method of  claim 57 , further comprising expressing the nucleic acid encoding the antibody to the carbohydrate antigen in a host cell, thereby producing an antibody to carbohydrate antigen. 
     
     
         59 . The method of  claim 56 , wherein the antibody is a monoclonal antibody, a polyclonal antibody, or a humanized antibody. 
     
     
         60 - 63 . (canceled) 
     
     
         64 . The method of  claim 56 , wherein the carbohydrate structure is administered with an adjuvant. 
     
     
         65 . The method of  claim 56 , wherein the carbohydrate antigen is a tumor-associated carbohydrate antigen. 
     
     
         66 . The method of  claim 56 , wherein the carbohydrate antigen is selected from the group consisting of GD2, GD3, GD1b, GT1b, fucosyl-GM1, GloboH, polysialic acid (PSA), GM2, GM3, sialyl-LewisX, sialyl-LewisY, sialyl-LewisA, sialyl-LewisB, and LewisY. 
     
     
         67 . The method of  claim 56 , wherein
 (a) P is a cycloalkyl, heterocyclyl, or heteroaryl group;   (b) L is selected from the group consisting of a hydrocarbon linker, a polyamine linker, a peptide linker, a synthetic polymer, or a covalent bond; and/or   (c) M is selected from the group consisting of branched polymers; nucleic acids; polyamines; polypeptides; polysaccharides, and micelles.   
     
     
         68 . The method of  claim 67 , wherein
 (a) P is selected from the group consisting of (3-aminomethyl)cyclopentylamine, cyclopentane-1,3-diyldimethanamine, 3-(aminomethyl)cyclopentanamine, quinoline-3,7-diamine, 4-aminoquinolin-8-ol, quinoline-4,8-diol, quinoline-4,8-diamine, isoquinoline-4,8-diamine, pyridine-2,6-dicarboxylic acid, triazine, imidazole, morpholino, and 4-(aminomethyl)piperidine;   (b) the hydrocarbon linker is a C2-C20 alkyl, a C2-C20 alkenyl, or a C2-C20 alkynyl;   (c) the polyamine linker is ethylene diamine, putrecine, cadaverine, spermidine, or spermine;   (d) the peptide linker is a polypeptide is 2 and 10 amino acids in length;   (e) the synthetic polymer is a polyether; and/or   (f) the covalent bond is an amide, ester, ether, azide, isothiocyanate, or disulfide bond.   
     
     
         69 . The method of  claim 67 , wherein the polyamine is PAMAM. 
     
     
         70 . The method of  claim 56 , wherein x is 4 or 8. 
     
     
         71 . The method of  claim 57 , wherein the antibody is a monoclonal antibody or a humanized antibody. 
     
     
         72 . The method of  claim 57 , wherein the carbohydrate structure is administered with an adjuvant. 
     
     
         73 . The method of  claim 57 , wherein the carbohydrate antigen is a tumor-associated carbohydrate antigen. 
     
     
         74 . The method of  claim 57 , wherein the carbohydrate antigen is selected from the group consisting of GD2, GD3, GD1b, GT1b, fucosyl-GM1, GloboH, polysialic acid (PSA), GM2, GM3, sialyl-LewisX, sialyl-LewisY, sialyl-LewisA, sialyl-LewisB, and LewisY. 
     
     
         75 . The method of  claim 57 , wherein
 (a) P is a cycloalkyl, heterocyclyl, or heteroaryl group;   (b) L is selected from the group consisting of a hydrocarbon linker, a polyamine linker, a peptide linker, a synthetic polymer, or a covalent bond; and/or   (c) M is selected from the group consisting of branched polymers; nucleic acids; polyamines; polypeptides; polysaccharides, and micelles.   
     
     
         76 . The method of  claim 75 , wherein
 (a) P is selected from the group consisting of (3-aminomethyl)cyclopentylamine, cyclopentane-1,3-diyldimethanamine, 3-(aminomethyl)cyclopentanamine, quinoline-3,7-diamine, 4-aminoquinolin-8-ol, quinoline-4,8-diol, quinoline-4,8-diamine, isoquinoline-4,8-diamine, pyridine-2,6-dicarboxylic acid, triazine, imidazole, morpholino, and 4-(aminomethyl)piperidine;   (b) the hydrocarbon linker is a C2-C20 alkyl, a C2-C20 alkenyl, or a C2-C20 alkynyl;   (c) the polyamine linker is ethylene diamine, putrecine, cadaverine, spermidine, or spermine;   (d) the peptide linker is a polypeptide is 2 and 10 amino acids in length;   (e) the synthetic polymer is a polyether; and/or   (f) the covalent bond is an amide, ester, ether, azide, isothiocyanate, or disulfide bond.   
     
     
         77 . The method of  claim 75 , wherein the polyamine is PAMAM. 
     
     
         78 . The method of  claim 57 , wherein x is 4 or 8.