Carbohydrate tethering at cell surfaces to induce immune response

1. A method of inducing an immune response in a diseased tissue in a subject, comprising administering to a subject a composition comprising a carbohydrate epitope and a pHLIP® peptide,

wherein said composition comprising the formula of Carb-Linker-Pept

wherein “Carb” is a carbohydrate epitope;

wherein “Linker” is a non-cleavable linker compound or a membrane non-inserting end of the pHLIP® peptide further comprises an amino acid extension;

wherein “Pept” is a pHLIP® peptide comprising the sequence

AXDDQNPWRAYLDLLFPTDTLLLDLLW (SEQ ID NO: 481) or

AXDQDNPWRAYLDLLFPTDTLLLDLLW (SEQ ID NO: 482), where “X” is a functional group, selected from a lysine, a cysteine, a serine, a threonine, or an Azido-containing amino acid;

wherein each “-” is a covalent bond.

2. The method of claim 1 , wherein said carbohydrate epitope and said peptide are connected by a non-cleavable linker or by an extension of the pHLIP® peptide membrane non-inserting terminus.

3. The method of claim 2 , wherein said pHLIP® peptide extension is a poly-Glycine peptide.

4. The method of claim 1 , wherein said linker comprises a polyethylene glycol (PEG) polymer, wherein the PEG polymer ranges from 4 to 24 PEG units.

5. The method of claim 4 , wherein said linker comprises a polyethylene glycol polymer.

6. The method of claim 4 , wherein said polymer ranges in size from 200 Daltons to 20 kiloDaltons.

7. The method of claim 1 , wherein said carbohydrate epitope comprises a blood antigen.

8. The method of claim 1 , wherein said composition comprises 2 or more pHLIP® peptides.

9. The method of claim 1 , wherein said composition comprises 2 or more carbohydrate epitopes.

10. The method of claim 9 , wherein the 2 carbohydrate epitopes are linked to a single pHLIP® peptide.

11. The method of claim 1 , wherein said composition comprising the formula of Carb-Linker-Pept-Linker-Carb

wherein “Carb” is a carbohydrate epitope;

wherein “Linker” is a polyethylene glycol linker;

wherein “Pept” is a pHLIP® peptide comprising the sequence

Ac-AKQNDDQNKPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO: 470) or

Ac-AKQNDNDNKPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO: 479) or

ACQNDDQNCPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO: 471) or

ACQNDNDNCPWRAYLDLLFPTDTLLLDLLWA (SEQ ID NO: 480)

wherein each “-” is a covalent bond.

12. The method of claim 1 , wherein said subject comprises a solid tumor.

13. The method of claim 1 , wherein said composition is injected directly into a tumor mass.

14. The method of claim 1 , wherein said composition is systemically administered.

15. The method of claim 1 , wherein a biological effect of said composition is at least 20% greater than that delivered in the absence of said composition.

16. The method of claim 1 , wherein said composition targets preferentially to a diseased tissue compared to a healthy tissue, thereby minimizing damage to said healthy tissue.

17. The method of claim 1 , wherein the carbohydrate epitope is delivered to a cell surface of the diseased tissue.

18. The method of claim 1 , wherein the carbohydrate epitope is preferentially inserted into a cell membrane of the diseased tissue.

19. The method of claim 1 , wherein the carbohydrate epitope comprises a glycan comprising an N-linked glycan, an O-linked glycan, or any combination thereof.

20. The method of claim 19 , wherein the glycan comprises Galactose-α-1,3-Galactose or derivatives thereof.

21. The method of claim 19 , wherein the carbohydrate epitope comprises a plurality of glycans.

22. The method of claim 19 , wherein the glycan comprises tri-Gal or derivatives thereof.

23. The method of claim 19 , wherein the N-linked glycan and the O-linked glycan comprises the core structure GlcNAc2Man3, Mannose-N-acetylgalactosamine [(Man)3(GlcNAc)2], α-rhamnose, Globo H, or sialic acid or derivatives thereof.

24. The method of claim 1 , wherein said method comprises placement of said carbohydrate epitope on tumor cell of said subject.