Scaffolds for cell collection or elimination

• US 10,695,468 B2
• Filed: 09/06/2017
• Issued: 06/30/2020
• Est. Priority Date: 06/21/2007
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Mooney, David J., Ali, Omar Abdel-Rahman
• Primary Examiner(s): Cabral, Robert S
• Application Number:
  US15/696,938
• Publication Number:
  US 20180036454A1
• Time in Patent Office: 1,028 Days
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/44 Radioisotopes, radionuclides
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/10 Anthelmintics

Abstract

A device that includes a scaffold composition and a bioactive composition with the bioactive composition being incorporated therein or thereon, or diffusing from the scaffold composition such that the scaffold composition and/or a bioactive composition captures and eliminates undesirable cells from the body a mammalian subject. The devices mediate active recruitment, sequestration, and removal or elimination of undesirable cells from their host.

Claims

1. A method of removing or eliminating an autoimmune cell from a mammalian subject, comprising

a) administering to the subject a device comprising a hydrogel composition and a bioactive composition, wherein the bioactive composition is incorporated into or conjugated onto the hydrogel composition, wherein the hydrogel composition comprises a polymer matrix and pores, and wherein the bioactive composition comprises a self-antigen pre-isolated from the subject;

b) exposing the autoimmune cell to the self-antigen, thereby recruiting the autoimmune cell to the hydrogel composition, wherein the autoimmune cell is predisposed to recognize the self-antigen as foreign;

c) capturing the autoimmune cell within the hydrogel composition, thereby sequestering the autoimmune cell from the host environment; and

d) removing or eliminating the captured autoimmune cell from the subject.

2. The method of claim 1, wherein the device is administered orally, systemically, intravenously, intraperitoneally, by intramuscular injection, by lumbar puncture to access cerebral spinal fluid, subcutaneously, transcutaneously, or surgically.

3. The method of claim 1, further comprising the step of collecting the device from the subject.

4. The method of claim 1, wherein the device is not collected from the subject.

5. The method of claim 1, wherein the self-antigen is isolated from a tissue of the subject.

6. The method of claim 1, wherein the self-antigen is a surface antigen.

7. The method of claim 1, wherein the subject has an autoimmune disease.

8. The method of claim 7, wherein the autoimmune disease is multiple sclerosis.

9. The method of claim 7, wherein the autoimmune disease is diabetes.

10. The method of claim 1, further comprising killing the sequestered autoimmune cell within the hydrogel composition.

11. The method of claim 10, wherein the sequestered autoimmune cell is killed by exposure to the hydrogel composition.

12. The method of claim 1, wherein the device further comprises a cell-death inducing agent.

13. The method of claim 12, further comprising killing the sequestered autoimmune cell by exposure to the cell-death inducing agent.

14. The method of claim 12, wherein the cell-death inducing agent comprises an engineered virus, a humanized monoclonal antibody to activate the immune system, a pro-apoptotic ligand, a radioactive isotope, a toxin, or a chemotherapeutic agent.

15. The method of claim 14, wherein the pro-apoptotic ligand comprises FasL, TNF, TRAIL, or a caspase activator.

16. The method of claim 14, wherein the radioactive isotope comprises Bismuth-213, Holmium-66, Iodine-125, Iodine-131, or Lutetium-177.

17. The method of claim 14, wherein the toxin comprises a hemotoxin, a necrotoxin, or a neurotoxin.

18. The method of claim 1, wherein the polymer comprises poly(lactide-co-glycolide)(PLGA).

19. The method of claim 1, wherein the size of the pores is less than about 10 nm, in the range of 100 nm to 2 μ

M, or greater than about 20 μ

M in diameter.

20. The method of claim 17, wherein the size of the pores is about 400 μ

M to 500 μ

M in diameter.

21. The method of claim 1, wherein the bioactive composition further comprises an additional cell-attractant.

22. The method of claim 21, wherein the cell attractant is selected from the group consisting of a multivalent acrylamide polymer linked to a sugar, a polylysine linked to a sugar, a cytokine, a chemokine, or a combination thereof.

23. The method of claim 22, wherein the cell attractant comprises a cytokine, a chemokine, or a combination thereof.

24. The method of claim 1, wherein the bioactive composition further comprises a signaling protein to either induce cell death or prevent further immune responses.

25. The method of claim 1, wherein the captured autoimmune cell is removed or eliminated by degradation of the captured autoimmune cell within the hydrogel composition.

26. The method of claim 1, wherein the captured autoimmune cell is removed or eliminated by collection of the hydrogel composition from the subject.