Glycosylated specificity exchangers
The present invention is directed to ligand/receptor and antigen/antibody specificity exchangers comprising a saccharide or glycoconjugate. Methods of making these specificity exchangers and methods of using said specificity exchangers to treat or prevent human disease are described herein.
1. A method of binding an anti-gal antibody to a cancer cell present in a subject comprising:
providing an isolated glycoconjugate to a subject that has an anti-gal antibody, wherein said isolated glycoconjugate comprises:
a first domain that is a ligand for a receptor on the cancer cell present in said subject or an amino acid sequence of an antibody that binds the cancer cell present in said subject; and
a second domain that has at least one Gal α(1,3)Gal saccharide synthetically conjugated to said ligand or said amino acid sequence of an antibody, wherein said at least one Gal α(1,3)Gal saccharide is directly joined to the first domain at one amino acid, such that said first domain binds to said cancer cell and said second domain binds to said anti-gal antibody, thereby generating a complex in said subject that comprises said anti-gal antibody, said glycoconjugate, and said cancer cell.
2. The method according to claim 1 , wherein the glycoconjugate comprises a ligand for a receptor on the cancer cell.
3. The method according to claim 1 , wherein the glycoconjugate comprises an amino acid sequence of an antibody that binds the cancer cell.
4. The method according to claim 3 , wherein the amino acid sequence encodes a complementarity determining region (CDR) of the antibody.
5. The method according to claim 1 , wherein the first domain is between 3-200 amino acids in length.
6. The method according to claim 1 , wherein the first domain is between 5-100 amino acids in length.
7. The method according to claim 1 , wherein the first domain is between 8-50 amino acids in length.
8. The method according to claim 1 , wherein the first domain is between 10-25 amino acids in length.
9. The method according to claim 1 , wherein said at least one Gal α(1,3)Gal saccharide is directly joined to the first domain at a hydroxylated amino acid.
10. The method according to claim 1 , wherein a plurality of Gal α(1,3)Gal saccharides are joined to the first domain.
11. The method according to claim 1 , wherein said glycoconjugate further comprises a peptide sequence that is recognized as non-self by existing antibodies in the subject.
12. A method of generating a complex that comprises an anti-gal antibody, an isolated glycoconjugate, and a cancer cell in a subject comprising:
(i) identifying a subject that has a cancer cell and an anti-gal antibody;
(ii) providing to said subject an isolated glycoconjugate that comprises:
a first domain that is a ligand for a receptor on the cancer cell or an amino acid sequence of an antibody that binds the cancer cell; and
a second domain that has at least one Gal α(1,3)Gal saccharide synthetically conjugated to said ligand or said amino acid sequence of an antibody, wherein said at least one Gal α(1,3)Gal saccharide is directly joined to the first domain at one amino acid, such that said first domain binds to said cancer cell and said second domain binds to said anti-gal antibody, thereby generating a complex that comprises said anti-gal antibody, said glycoconjugate, and said cancer cell.
13. The method according to claim 12 , wherein said at least one Gal α(1,3)Gal saccharide is directly joined to the first domain at a hydroxylated amino acid.
14. A method for forming a complex, comprising:
(i) administering to a subject a bifunctional binding moiety comprising a first domain that is a ligand for a receptor on a cancer cell or an amino acid sequence of an antibody that binds a cancer cell and a second domain that has at least one Gal α(1,3)Gal saccharide synthetically conjugated to said ligand or said amino acid sequence of an antibody, wherein said at least one Gal α(1,3)Gal saccharide is directly joined to the first domain at one amino acid;
(ii) binding said first domain to a cancer cell in the subject; and
(iii) binding said second domain to anti-gal antibody in the subject, thereby forming said complex.
15. The method according to claim 14 , wherein said at least one Gal α(1,3)Gal saccharide is directly joined to the first domain at a hydroxylated amino acid.
16. The method according to claim 1 , wherein the glycoconjugate is a peptide.
17. The method according to claim 12 , wherein the glycoconjugate comprises a ligand for a receptor on the cancer cell.
18. The method according to claim 12 , wherein the glycoconjugate comprises an amino acid sequence of an antibody that binds the cancer cell.
19. The method according to claim 18 , wherein the amino acid sequence encodes a complementarity determining region (CDR) of the antibody.
20. The method according to claim 12 , wherein the first domain is between 3-200 amino acids in length.
21. The method according to claim 12 , wherein the first domain is between 5-100 amino acids in length.
22. The method according to claim 12 , wherein the first domain is between 8-50 amino acids in length.
23. The method according to claim 12 , wherein the first domain is between 10-25 amino acids in length.
24. The method according to claim 12 , wherein a plurality of Gal α(1,3)Gal saccharides are joined to the first domain.
25. The method according to claim 12 , wherein said glycoconjugate further comprises a peptide sequence that is recognized as non-self by existing antibodies in the subject.
26. The method according to claim 12 , wherein the glycoconjugate is a peptide.
27. The method according to claim 14 , wherein the bifunctional binding moiety comprises a ligand for a receptor on a cancer cell.
28. The method according to claim 14 , wherein the bifunctional binding moiety comprises an amino acid sequence of an antibody that binds a cancer cell.
29. The method according to claim 28 , wherein the amino acid sequence encodes a complementarity determining region (CDR) of the antibody.
30. The method according to claim 14 , wherein the first domain is between 3-200 amino acids in length.
31. The method according to claim 14 , wherein the first domain is between 5-100 amino acids in length.
32. The method according to claim 14 , wherein the first domain is between 8-50 amino acids in length.
33. The method according to claim 14 , wherein the first domain is between 10-25 amino acids in length.
34. The method according to claim 14 , wherein a plurality of Gal α(1,3)Gal saccharides are joined to the first domain.
35. The method according to claim 14 , wherein said bifunctional binding moiety further comprises a peptide sequence that is recognized as non-self by existing antibodies in the subject.
36. The method according to claim 14 , wherein the bifunctional binding moiety is a peptide.