Scaffolds for cell collection or elimination

• US 9,770,535 B2
• Filed: 06/11/2008
• Issued: 09/26/2017
• 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:
  US12/665,761
• Publication Number:
  US 20110020216A1
• Time in Patent Office: 3,394 Days
• Field of Search: 424 111, 4241301, 4241591, 4241601, 4241611, 4241641, 4241651, 4241661, 4241671, 4241681, 4241691, 4241701, 4241721, 424409, 424 7835, 424 931, 424 932, 424402, 435243, 435 29, 435 5, 514 23, 514 24, 514 26, 514 27, 514 28, 514 29, 514 31, 514 32, 514 33, 514 34, 514 36, 514 37, 514 38, 514 42, 514 44, 514 46, 514 54, 514 56, 623 142
• 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 a cancer cell from a mammalian subject, comprising

a) administering to the subject, a device comprising a scaffold composition and a bioactive composition, said bioactive composition being incorporated into or conjugated onto said scaffold composition, wherein said scaffold composition comprises a polymer matrix and pores, and wherein the bioactive composition comprises a cell attractant and a cell death-inducing agent, wherein said scaffold composition does not comprise cells prior to said administering step,

b) exposing said cancer cell to said cell attractant, thereby recruiting the cancer cell to the scaffold composition,

c) capturing said cancer cell within said scaffold composition, thereby sequestering said cancer cell from the host environment, and

d) killing the sequestered cancer cell within said scaffold composition by exposure to the scaffold composition or to the cell death-inducing agent, wherein the sequestered cancer cell is killed without removing the device from the subject, thereby removing or eliminating the cancer cell from the subject.

2. The method of claim 1, wherein the cell attractant disseminates from said scaffold composition.

3. The method of claim 1, wherein said device is administered orally, systemically, by lumbar puncture to access cerebral spinal fluid, subcutaneously, transcutaneously, as an arterial stent, or surgically.

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

5. The method of claim 1, wherein the bioactive composition comprises an antigen or an adhesive compound.

6. The method of claim 1, wherein the cancer cell comprises a metastatic cancer cell.

7. The method of claim 1, wherein the cancer cell displays a surface antigen.

8. The method of claim 1, wherein the cell attractant comprises a cytokine or a chemokine.

9. The method of claim 8, wherein the cytokine or chemokine attracts metastatic cancer cells, immune cells, or both metastatic cancer cells and immune cells.

10. The method of claim 1, wherein the bioactive composition comprises an inhibitor of chemokine receptor activity.

11. The method of claim 10, wherein the inhibitor comprises AMD3100, T22, TN14003, T140, TC14012, 4F-bTE, BX-471, Met-CCL5, TAK779, or TAK220.

12. The method of claim 1, wherein the bioactive composition comprises an anti-metastatic compound.

13. The method of claim 1, wherein the device adheres to a surface protein on the cancer cell, wherein the surface protein is unique to cancer cells.

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

15. 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.

16. The method of claim 15, wherein the size of the pores is about 400 μ

M to 500 μ

M in diameter.

17. The method of claim 1, wherein the cell death-inducing agent comprises a compound that prevents or arrests cell division, 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.

18. The method of claim 17, wherein the pro-apoptotic ligand comprises FasL, TNF, TRAIL, or a caspase activator.

19. The method of claim 17, wherein the radioactive isotope comprises Bismuth-213, Holmium-66, Iodine-125, Iodine-131, or Lutetium-177.

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

21. The method of claim 17, wherein the compound that prevents or arrests cell division comprises Dacarbazine, Fluorouracil, Fludarabine, Gemcitabine, Trastuzumab, Hydroxyurea, Idarubicin, Ifosfamide, Irinotecan, Cladribine/Leustatin, Mercaptopurine, Methotrexate, Mithramycin, Mitomycin, Mitoxanthrone, Navelbine, Nitrogen Mustard, Rituxan, Paclitaxel, Docetaxel, Topotecan, Velban, Vincristine, or Etoposide.

22. The method of claim 1, wherein the cell attractant comprises a multivalent acrylamide polymer linked to a sugar, a polylysine linked to a sugar, or an amino acid.

23. The method of claim 22, wherein the sugar comprises galactose, fructose, or ribose.

24. The method of claim 22, wherein the amino acid comprises aspartate, leucine, or serine.

25. The method of claim 1, wherein the device is administered by implanting into a tissue of the subject which is not blood tissue.

26. The method of claim 25, wherein the device is administered by implanting into a site selected from the group consisting of adipose tissue, gastrointestinal tract, lymphatic fluid, primary tumor site, and cerebral spinal fluid.

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