SCAFFOLDS FOR CELL COLLECTION OR ELIMINATION

• US 20110020216A1
• Filed: 06/11/2008
• Published: 01/27/2011
• 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: Ali, Omar abdel-Rahman, Mooney, David James
• Granted Patent: US 9,770,535 B2
• Time in Patent Office: Days
• US Class Current: 424/1.11
• 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 device comprising a scaffold composition and bioactive composition, said bioactive composition being incorporated into or conjugated onto said scaffold composition, wherein said scaffold composition or said bioactive composition captures an undesirable cell, or wherein said scaffold composition or said bioactive composition destroys an undesirable cell.

12. The device of claim 1, wherein said scaffold composition has one or more of the following characteristics:

(a) comprises a non-biodegradable material;

(b) comprises a non-biodegradable material selected from the group consisting of a metal, a plastic polymer, or a silk polymer;

(c) comprises a biocompatible material;

(d) is non-toxic;

(e) is non-immunogenic;

(f) contains a solid external surface;

(g) contains a porous external surface;

(h) contains a solid internal surface;

(i) contains a porous internal surface;

or

(j) comprises one or more compartments.

16. The device of claim 1, wherein said bioactive composition is covalently or non-covalently linked to the scaffold composition.

17. The device of claim 1, wherein said bioactive composition comprises an element either covalently or non-covalently bonded to the surface of the scaffold composition, with means to bind a target cell.

18. The device of claim 17, wherein said element is a secreted or membrane-bound amino acid, peptide, protein, polymer, or chemical.

25. The device of claim 12, wherein said external surface, said internal surface or both said external surface and internal surface are porous, wherein said pore size is less than about 10 nm, in the range of about 100 nm-20 μ

m in diameter, or greater than about 20 μ

m.

53. The device of claim 1, wherein said bioactive composition comprises a multivalent acrylamide polymer, polylysine tagged with a sugar or an amino acid, a cytokine, a chemokine, an adhesin, a polysaccharide, a sugar sialic acid, a capsid-binding protein, a viral attachment protein, an isolated plasma membrane fraction from a cellular target, an integrin, an Ig superfamily member, a cadherin, a selectin, a phagocytic cell, an engineered virus, an antibody, a pro-apoptotic ligand, a caspase-activator, a radioactive isotope, a toxin, or a chemotherapy agent.

54. The device of claim 1, wherein said bioactive composition comprises fibronectin, laminin, collagen, thrombospondin 1, vitronectin, elastin, tenascin, aggrecan, agrin, bone sialoprotein, cartilage matrix protein, fibrinogen, fibrin, fibulin, a mucin, entactin, osteopontin, plasminogen, restrictin, serglycin, SPARC/osteonectin, versican, von Willebrand Factor, polysaccharide heparin sulfate, a connexin, collagen, a RGD (Arg-Gly-Asp) peptide or cyclic peptide, a YIGSR (Tyr-Ile-Gly-Ser-Arg) peptide or cyclic peptide, a glycosaminoglycan (GAG), hyaluronic acid (HA), condroitin-6-sulfate, an integrin ligand, a neural cell adhesion molecule (NCAM), an intercellular adhesion molecule (ICAM), a vascular cell adhesion molecule (VCAM-1), a platelet-endothelial cell adhesion molecule (PECAM-1), L1 or CHL1.

2-5. -5. (canceled)

6. A method of making a scaffold, comprising providing a scaffold composition, covalently linking said scaffold composition with a first bioactive composition comprising proteins with means for binding an undesirable cell, and contacting said scaffold composition with a second bioactive composition, wherein said second bioactive composition is covalently or non-covalently associated with said scaffold composition wherein said second bioactive composition comprises a cytotoxic or cytostatic agent.

7. The method of claim 6, wherein said linking and contacting steps are repeated to yield a plurality of layers, wherein said second bioactive composition comprises a combination of compounds with means to eliminate an undesirable cell.

19. The method of claim 7, wherein said undesirable cell comprises a host cell, a foreign cell, a stem cell, a differentiated cell, a dividing cell, a migrating cell or a circulating cell.

20. The device of claim 19, wherein said host cell displays host surface antigens or wherein said foreign cell displays non-host surface antigens.

33. The method of claim 6, wherein said second bioactive composition is a protein, an organic compound, an inorganic compound, a radioisotope, an antibiotic compound, an antiviral compound, an antiparasitic compound, an engineered virus, an activated immune cell, a toxin, a natural compound or a synthetic compound.

8. A method of removing or eliminating a microorganism or target cell from a mammal, comprising administering to a subject exposed to or infected by said microorganism or target cell, a device comprising a scaffold composition and bioactive composition, said bioactive composition being incorporated into or conjugated onto said scaffold composition, wherein said scaffold composition or bioactive composition captures said microorganism or target cell, thereby sequestering said microorganism or target cell from the host environment.

9. The method of claim 8, further comprising the step of exposing said microorganism or target cell to said bioactive composition, wherein said scaffold composition or said bioactive composition induces death of said microorganism or target cell.

11. The method of claim 8, wherein said scaffold composition disseminates said bioactive composition.

26. The method of claim 8, wherein said microorganism is a virus, bacteria, fungus, protozoan, worm, a spore, an immature cell, or a vegetative cell.

27. The method of claim 26, wherein said microorganism is:

(a) a virus selected from the group consisting of adenoviruses, herpesviruses, poxviruses, parvoviruses, papovaviruses, hepadnaviruses, orthomyxoviruses, paramyxoviruses, coronaviruses, picornaviruses, reoviruses, togaviruses, flaviviruses, arenaviruses, rhabdoviruses, and retroviruses,

(b) a bacteria selected from the group consisting of Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria gonorrhoeae, Neisseria meningitides, Corynebacteria diphtheriae, Bacillus anthracis, Listeria monocytogenes, Escherichia coli, Salmonella typhimurium, Salmonella typhae, ShiellaCalobacter Yersinia Pseudomonas aeruginosa, Brucella Haemophilus, influenzae, Legionella, Bordetella, Clostridium tetani, Clostridium botulinum, Clostridium perfringens, Treponema pallidum, Borrelia burgdorferi, Leptospira interrogans, Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium avium, Rickettsia prowazekii, Chlamydia trachomatis, and Mycoplasma pneumoniae;

(c) a fungus selected from the group consisting of Candida albicans, Cryptococcus neoformans, Aspergillus, Histoplasma capsulatum, Coccidioides immitis and Pneumocystis carinii;

(d) a protozoan selected from the group consisting of Entamoeba histolytica, Giardia, Leishmania, Plasmodium (falciparum, vivax), Trypanosoma (brucei), Mxoplasma gondii, and Cryptosporidium;

or

(e) a worm selected from the group consisting of Trichuris trichiura, Trichinella spiralis, Enterobius vermicularis, Ascaris lumbricoides, Ancylostoma, Stron loides Filaria Onchocerca volvulus Loa loa, Dracuncula medinensis, Schistosoma (mansoni), and Clonorchis sinensis.

46. The method of claim 8, wherein said device is administered orally, systemically, by lumbar puncture to access cerebral spinal fluid, subcutaneously, transcutaneously, as an arterial stent, or surgically.

52. The method of claim 8, further comprising the step of collecting said device from the mammal, thereby allowing the composition of captured cells to be analyzed or identified.

10. (canceled)

13-15. -15. (canceled)

21-24. -24. (canceled)

28-32. -32. (canceled)

34-45. -45. (canceled)

47-51. -51. (canceled)