Albumin binding peptide conjugates and methods thereof
The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.
1. A method for increasing an immune response in a subject comprising administering to the subject an effective amount of a composition, wherein the composition comprises a conjugate comprising:
(a) an albumin binding peptide; and
(b) an immunomodulatory molecule,
wherein the albumin binding peptide is operatively coupled to the immunomodulatory molecule with or without a linker domain;
such that the composition increases the immune response in the subject.
2. The method of claim 1 , wherein the immunomodulatory molecule further comprises a peptide antigen or an immunostimulatory oligonucleotide.
3. The method of claim 1 , wherein the method further comprises administering multiple doses of the conjugate.
4. The method of claim 1 , wherein the method further comprises administering the conjugate at various locations.
5. The method of claim 1 , wherein the method further comprises administering the conjugate directly to a site in need of an immune response.
6. The method of claim 1 , wherein the subject has cancer or an infectious disease.
7. The method of claim 1 , wherein the albumin binding peptide is covalently linked to the immunomodulatory molecule, or the albumin binding peptide is operatively coupled to the immunomodulatory molecule via a linker domain.
8. The method of claim 7 , wherein the linker domain comprises a Gly-Ser linker or a polyethylene glycol (PEG) linker.
9. The method of claim 8 , wherein the Gly-Ser linker is a (Gly4Ser)n (SEQ ID NO: 44) linker, and wherein n is 1-6.
10. The method of claim 8 , wherein the PEG linker is a PEG 2000 linker.
11. The method of claim 1 , wherein the immunomodulatory molecule comprises an immunomodulatory oligonucleotide.
12. The method of claim 11 , wherein the immunomodulatory oligonucleotide is CpG DNA.
13. The method of claim 1 , wherein the albumin binding peptide comprises the amino acid sequence DICLPRWGCLW (SEQ ID NO: 9).
14. The method of claim 1 , wherein the immunomodulatory molecule is a peptide antigen.
15. The method of claim 14 , wherein the peptide antigen is a cancer antigen or a melanoma antigen.
16. The method of claim 14 , wherein the peptide antigen is a tumor-associated antigen.
17. The method of claim 14 , wherein the peptide is generated from a viral or bacterial antigen or an allergen or an environmental antigen.
18. The method of claim 1 , wherein said composition further comprises a pharmaceutically acceptable carrier or excipient.
19. A method for increasing an immune response in a subject comprising administering to the subject an effective amount of a vaccine comprising a composition for directing immunomodulatory molecules to the lymphatic system so as to increase the immune response in the subject and a pharmaceutically acceptable carrier or excipient, wherein the composition comprises a conjugate comprising:
(a) an albumin binding peptide; and
(b) an immunomodulatory molecule,
wherein the albumin binding peptide is operatively coupled to the immunomodulatory molecule with or without a linker domain.
20. The method of claim 19 , wherein the immunomodulatory molecule further comprises a peptide antigen or an immunostimulatory oligonucleotide.