Injectable cryogel vaccine devices and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9675561-B2
Application number	US-201414166689-A
Country	US
Kind code	B2
Filing date	Jan 28, 2014
Priority date	Apr 28, 2011
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

The invention provides polymer compositions for cell and drug delivery.

First claim

What is claimed is:

1. An injectable device comprising a cell-adhesive, highly crosslinked cryogel composition comprising open interconnected macropores,
wherein said cryogel composition comprises at least 75% pores,
wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle,
wherein said cryogel composition comprises a crosslinked gelatin polymer, wherein said gelatin is methacrylated,
wherein said cryogel composition comprises a methacrylated gelatin concentration of 0.5% to 1.4% (w/v), and
wherein said cryogel composition comprises a live attenuated breast cancer cell in one or more of said open interconnected pores.

2. The device of claim 1 , wherein the device recruits cells into the cryogel composition upon injection into a subject.

3. The device of claim 2 , wherein the cryogel composition is degraded by the recruited cells.

4. The device of claim 1 , wherein the cryogel composition is formed by cryopolymerization of methacrylated gelatin.

5. The device of claim 4 , wherein the cryogel composition further comprises a methacrylated alginate macromonomer.

6. The device of claim 1 , wherein said cryogel composition comprises a biomolecule in one or more of said open interconnected pores.

7. The device of claim 6 , wherein said biomolecule comprises a small molecule, nucleic acid, or protein.

8. The device of claim 7 , wherein said protein comprises granulocyte-macrophage colony-stimulating factor (GM-CSF).

9. The device of claim 7 , wherein said nucleic acid comprises a CpG nucleic acid oligonucleotide (CpG-ODN).

10. The device of claim 1 , wherein the device is between 100 um 3 to 100 mm 3 in size.

11. A method for eliciting an immune response, comprising injecting the device of claim 1 into a subject, wherein an immune response is elicited against the live attenuated breast cancer cell.

12. The method of claim 11 , wherein the device is injected into the subject one to 5 times in the lifetime of the subject.

13. The method of claim 11 , wherein the injected device comprises at least 0.5×10 6 immune cells at least 1 day after injection into the subject.

14. The method of claim 11 , wherein the injected device comprises 10 7 or fewer cells 15 days or more after injection.

15. The method of claim 11 , wherein the injected device, a tissue within 10 cm of the injected device, or both comprises an elevated level of a cytokine compared to the level of the cytokine at a site in the subject more than 10 cm away from the injected device.

16. The method of claim 11 , wherein the device increases the survival time of at least 80% of subjects diagnosed with a cancer by at least 1 month compared to the survival time of untreated subjects, wherein increased survival time is determined by comparing the prognosis for survival in the subjects from a time period prior to administration of the device to the prognosis for survival in the subjects following administration of the device, wherein an increase in predicted survival time indicates that the treatment increased survival of the subjects following administration of the device.

17. The method of claim 11 , wherein the device reduces the rate of tumor growth in the subject compared to the rate of tumor growth in an untreated subject.

18. The device of claim 7 , wherein said nucleic acid comprises deoxyribonucleic acid (DNA).

19. The device of claim 1 , wherein the device is in the shape of a disc, cylinder, square, rectangle, or string.

20. The device of claim 1 , wherein said highly crosslinked cryogel composition comprises a crosslinking density of at least 50% polymer crosslinking.

21. The device of claim 1 , wherein said highly crosslinked cryogel composition comprises a crosslinking density of at least 50-100% polymer crosslinking.

22. The device of claim 1 , wherein said device comprises live attenuated HER-2/neu expressing breast cancer cells.

23. The device of claim 1 , wherein said live attenuated breast cancer cell is an irradiated breast cancer cell.

24. The device of claim 1 , wherein said cryogel composition comprises macropores having a diameter of 20 μm to 300 μm.

25. A syringe comprising an injectable device comprising a cell-adhesive, highly crosslinked cryogel composition comprising open interconnected pores,
wherein said cryogel composition comprises at least 75% pores,
wherein said cryogel composition is characterized by shape memory following deformation by compression,
wherein said cryogel composition comprises a crosslinked gelatin polymer, wherein said gelatin is methacrylated,
wherein said cryogel composition comprises a methacrylated gelatin concentration of 0.5% to 1.4% (w/v), and
wherein said cryogel composition comprises live attenuated breast cancer cells in one or more of said open interconnected pores.

26. The syringe of claim 25 , comprising a 16-gauge, an 18-gauge, a 22-gauge, a 24-gauge, a 26-gauge, a 28-gauge, a 30-gauge, a 32-gauge, or a 34-gauge needle.

27. The syringe of claim 25 , comprising an 18 to 30-gauge needle.

28. The syringe of claim 26 , wherein the device is between 1 mm 3 to 50 mm 3 in size.

29. The syringe of claim 26 , wherein 90% or more of the cancer cells survive passage of the device through the bore of the needle.

30. The syringe of claim 25 , wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle, such that said cryogel returns to its original undeformed three-dimensional shape less than one second after compression through the needle.

31. The syringe of claim 25 , wherein said cryogel composition comprises macropores having a diameter of 20 μm to 300 μm.

32. The method of claim 11 , wherein the device
(i) comprises live attenuated HER-2/neu expressing breast cancer cells, and
(ii) increases the level of HER-2/neu-specific IgG antibody in subjects diagnosed with a cancer by approximately 70-fold compared to untreated subjects.

33. The device of claim 1 , wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle such that said cryogel composition returns to its original undeformed three-dimensional shape less than one second after compression through the needle.

34. The device of claim 6 , wherein said biomolecule comprises a pathogen-associated molecular pattern (PAMP).

35. An injectable device comprising a cell-adhesive, highly crosslinked cryogel composition comprising open interconnected macropores,
wherein said cryogel composition comprises at least 75% pores,
wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle,
wherein said cryogel composition comprises a crosslinked gelatin polymer, wherein said gelatin is methacrylated, and
wherein said cryogel composition comprises a methacrylated gelatin concentration of 0.5% to 1.4% (w/v).

36. The device of claim 35 , wherein said cryogel composition comprises macropores having a diameter of 20 μm to 300 μm.

37. The device of claim 35 , wherein said cryogel composition is characterized by shape memory following deformation by compression through a needle, such

Assignees

• Harvard College

Inventors

• Bencherif Sidi A
• Sands Roger Warren
• Koshy Sandeep T
• Mooney David J

Classifications

• A61L2300/258

  Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids · CPC title

• A61L2300/252

  Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines · CPC title

• A61L27/56

  Porous materials, {e.g. foams or sponges} · CPC title

• A61K2039/55561

  CpG containing adjuvants; Oligonucleotide containing adjuvants · CPC title

• A61K2039/55522

  Cytokines; Lymphokines; Interferons · CPC title