Scaffolds for cell transplantation

• US 9,132,210 B2
• Filed: 03/24/2014
• Issued: 09/15/2015
• Est. Priority Date: 12/13/2005
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation), Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Mooney, David J., Ali, Omar Abdel-Rahman, Barros E Silva, Eduardo Alexandre, Kong, Hyun Joon, Hill, Elliot Earl Jr., Boontheekul, Tanyarut
• Primary Examiner(s): Long, Scott
• Application Number:
  US14/223,759
• Publication Number:
  US 20150024026A1
• Time in Patent Office: 540 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55522 Cytokines; Lymphokines; Interferons
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/55583 Polysaccharides
• CPC Class Codes: A61K 2039/6093 Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001156 Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]
• CPC Class Codes: A61K 39/00117 Mucins, e.g. MUC-1
• CPC Class Codes: A61K 39/001171 Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/00118 from embryonic or fetal origin
• CPC Class Codes: A61K 39/001182 Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61K 39/001184 Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
• CPC Class Codes: A61K 39/001186 MAGE
• CPC Class Codes: A61K 39/001191 Melan-A/MART
• CPC Class Codes: A61K 39/001192 Glycoprotein 100 [Gp100]
• CPC Class Codes: A61K 39/001195 Prostate specific membrane antigen [PSMA]
• CPC Class Codes: A61K 39/21 : Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61K 39/39 : characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/0024 : Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1647 : Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 2300/232 : Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
• CPC Class Codes: A61L 2300/252 : Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/412 : Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/414 : Growth factors
• CPC Class Codes: A61L 2300/426 : Immunomodulating agents, i.e. cytokines, interleukins, interferons
• CPC Class Codes: A61L 2300/438 : Antigens
• CPC Class Codes: A61L 2300/604 : Biodegradation
• CPC Class Codes: A61L 2300/606 : Coatings
• CPC Class Codes: A61L 2400/18 : Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 2430/30 : for muscle reconstruction
• CPC Class Codes: A61L 2430/34 : for soft tissue reconstruction
• CPC Class Codes: A61L 27/18 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 : Polysaccharides
• CPC Class Codes: A61L 27/3633 : Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/38 : containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3826 : Muscle cells, e.g. smooth muscle cells
• 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: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B33Y 80/00 : Products made by additive manufacturing
• CPC Class Codes: C12N 15/117 : Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• CPC Class Codes: C12N 2310/17 : Immunomodulatory nucleic acids
• CPC Class Codes: C12N 2320/32 : Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12N 2740/16034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A device that includes a scaffold composition and a bioactive composition with the bioactive composition being incorporated into or coated onto the scaffold composition such that the scaffold composition and/or a bioactive composition controls egress of a resident cell or progeny thereof. The devices mediate active recruitment, modification, and release of host cells from the material.

Claims

1. A cancer vaccine device comprising a scaffold composition comprising a polymer matrix and having open, interconnected macropores;

a granulocyte-macrophage colony stimulating factor (GM-CSF) that recruits immune cells selected from macrophages, T-cells, B-cells, NK cells, and dendritic cells;

a tumor antigen; and

an immune response-promoting bioactive factor comprising an oligonucleotide, wherein the GM-CSF, the tumor antigen, or the immune response-promoting bioactive factor is incorporated into or coated onto said scaffold composition, wherein said device further comprises an extracellular matrix (ECM) component, and wherein the ECM component comprises an arginine-glycine-aspartate (RGD) sequence.

2. The device of claim 1, wherein the GM-CSF, tumor antigen, or immune response-promoting bioactive factor is covalently linked to said scaffold composition.

3. The device of claim 1, wherein the tumor antigen comprises biopsy-extracted antigens.

4. The device of claim 1, wherein the tumor antigen comprises a tumor cell lysate.

5. The device of claim 1, wherein the scaffold composition degrades at a predetermined rate based on a physical parameter selected from the group consisting of temperature, pH, hydration status, and porosity.

6. The device of claim 1, wherein the scaffold composition comprises pores of greater than 100 μ

m in size.

7. The device of claim 6, wherein the scaffold composition comprises pores of 400-500 μ

m in size.

8. The device of claim 1, wherein the tumor is chosen from a central nervous system (CNS) cancer, CNS germ cell tumor, lung cancer, leukemia, multiple myeloma, renal cancer, malignant glioma, ovarian cancer, prostate cancer, medulloblastoma, melanoma, breast cancer, ovarian cancer, Karposi'"'"'s sarcoma, colon cancer, adenocarcinoma, brain cancer, testicular cancer, hepatocellular carcinoma, synovial sarcoma, and squamous cell carcinoma.

9. The device of claim 8, wherein the tumor is chosen from a melanoma, lung cancer, malignant glioma, and breast cancer.

10. The device of claim 1, wherein the device comprises PLGA microspheres.

11. The device of claim 1, wherein the device further comprises a vaccine adjuvant chosen from a chemokine, cytokine, and an antibody.

12. The device of claim 1, wherein the scaffold composition comprising open, interconnected macropores is made by gas foaming.

13. The device of claim 1, wherein the tumor antigen comprises a MAGE series of antigens, MART-1/melana, Tyrosinase, ganglioside, gp100, GD-2, 0-acetylated GD-3, GM-2, MUC-1, Sosl, Protein kinase C-binding protein, Reverse transcriptase protein, AKAP protein, VRK1, KIAA1735, T7-1, T11-3, T11-9, Homo Sapiens telomerase ferment (hTRT), Cytokeratin-19 (CYFRA21-1), SQUAMOUS CELL CARCINOMA ANTIGEN 1 (SCCA-1), (PROTEIN T4-A), SQUAMOUS CELL CARCINOMA ANTIGEN 2 (SCCA-2), Ovarian carcinoma antigen CA125 (1A1-3B) (KIAA0049), MUCIN 1 (TUMOR-ASSOCIATED MUCIN), (CARCINOMA-ASSOCIATED MUCIN), (POLYMORPHIC EPITHELIAL MUCIN), (PEM), (PEMT), (EPISIALIN), (TUMOR-ASSOCIATED EPITHELIAL MEMBRANE ANTIGEN), (EMA), (H23AG), (PEANUT-REACTIVE URINARY MUCIN), (PUM), (BREAST CARCINOMA-ASSOCIATED ANTIGEN DF3), CTCL tumor antigen sel-1, CTCL tumor antigen se14-3, CTCL tumor antigen se20-4, CTCL tumor antigen se20-9, CTCL tumor antigen se33-1, CTCL tumor antigen se37-2, CTCL tumor antigen se57-1, CTCL tumor antigen se89-1, Prostate-specific membrane antigen, 5T4 oncofetal trophoblast glycoprotein, Orf73 Kaposi'"'"'s sarcoma-associated herpesvirus, MAGE-Cl (cancer/testis antigen CT7), MAGE-B1 ANTIGEN (MAGE-XP ANTIGEN) (DAM10), MAGE-B2 ANTIGEN (DAME), MAGE-2 ANTIGEN, MAGE-4a antigen, MAGE-4b antigen, Colon cancer antigen NY-CO-45, Lung cancer antigen NY-LU-12 variant A, Cancer associated surface antigen, Adenocarcinoma antigen ART1, Paraneoplastic associated brain-testis-cancer antigen (onconeuronal antigen MA2;

paraneoplastic neuronal antigen), Neuro-oncological ventral antigen 2 (NOVA2), Hepatocellular carcinoma antigen gene 520, TUMOR-ASSOCIATED ANTIGEN CO-029, Tumor-associated antigen MAGE-X2, Synovial sarcoma, X breakpoint 2, Squamous cell carcinoma antigen recognized by T cell, Serologically defined colon cancer antigen 1, Serologically defined breast cancer antigen NY-BR-15, Serologically defined breast cancer antigen NY-BR-16, Chromogranin A, parathyroid secretory protein 1, DUPAN-2, CA 19-9, CA 72-4, CA 195, or Carcinoembryonic antigen (CEA).

14. The device of claim 1, wherein the immune response-promoting bioactive factor comprises a DNA molecule.

15. The device of claim 1, wherein the immune response-promoting bioactive factor comprises an RNA molecule.

16. The device of claim 1, wherein the immune response-promoting bioactive factor comprises a CpG rich oligonucleotide.

17. The device of claim 1, wherein the device is in a needle, endoscopic manipulator, catheter, surgical implantation tool, or minimally invasive surgical device.

18. The device of claim 1, wherein the polymer matrix comprises polylactic acid, polyglycolic acid, polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA) polymer, alginate, alginate derivative, gelatin, collagen, fibrin, agarose, hyaluronic acid, natural polysaccharide, synthetic polysaccharide, polyamino acid, polyester, polyanhydride, polyphosphazine, poly(vinyl alcohol), poly(alkylene oxide), modified styrene polymer, pluronic polyol, polyoxamer, poly(uronic acid), poly(vinylpyrrolidone).

19. The device of claim 1, wherein the polymer matrix comprises poly(lactic-co-glycolic acid) (PLGA).

20. A cancer vaccine device comprising a scaffold composition comprising a polymer matrix and having open, interconnected macropores;

a granulocyte-macrophage colony stimulating factor (GM-CSF) that recruits immune cells selected from macrophages, T-cells, B-cells, NK cells, and dendritic cells;

a tumor antigen; and

an immune response-promoting bioactive factor comprising an RNA molecule,

wherein the GM-CSF, the tumor antigen, or the immune response-promoting bioactive factor is incorporated into or coated onto said scaffold composition.

21. The device of claim 20, wherein said device further comprises an extracellular matrix (ECM) component.

22. The device of claim 20, wherein said ECM component comprises an arginine-glycine aspartate (RGD) sequence.

23. The device of claim 20, wherein the GM-CSF, tumor antigen, or immune response-promoting bioactive factor is covalently linked to said scaffold composition.

24. The device of claim 20, wherein the tumor antigen comprises biopsy-extracted antigens.

25. The device of claim 20, wherein the tumor antigen comprises a tumor cell lysate.

26. The device of claim 20, wherein the scaffold composition degrades at a predetermined rate based on a physical parameter selected from the group consisting of temperature, pH, hydration status and porosity.

27. The device of claim 20, wherein said scaffold composition comprises pores of greater than 100 μ

m in size.

28. The device of claim 27, wherein the scaffold composition comprises pores of 400-500 μ

m in size.

29. The device of claim 20, wherein the tumor is chosen from a central nervous system (CNS) cancer, CNS germ cell tumor, lung cancer, leukemia, multiple myeloma, renal cancer, malignant glioma, ovarian cancer, prostate cancer, medulloblastoma, melanoma, breast cancer, ovarian cancer, Karposi'"'"'s sarcoma, colon cancer, adenocarcinoma, brain cancer, testicular cancer, hepatocellular carcinoma, synovial sarcoma, and squamous cell carcinoma.

30. The device of claim 29, wherein the tumor is chosen from a melanoma, lung cancer, malignant glioma, and breast cancer.

31. The device of claim 20, wherein the device comprises PLGA microspheres.

32. The device of claim 20, wherein the device further comprises a vaccine adjuvant chosen from a chemokine, cytokine and an antibody.

33. The device of claim 20, wherein the scaffold composition comprising open, interconnected macropores is made by gas foaming.

34. The device of claim 20, wherein the tumor antigen comprises a MAGE series of antigens, MART-1/melana, Tyrosinase, ganglioside, gp100, GD-2, 0-acetylated GD-3, GM-2, MUC-1, Sosl, Protein kinase C-binding protein, Reverse transcriptase protein, AKAP protein, VRK1, KIAA1735, T7-1, T11-3, T11-9, Homo Sapiens telomerase ferment (hTRT), Cytokeratin-19 (CYFRA21-1), SQUAMOUS CELL CARCINOMA ANTIGEN 1 (SCCA-1), (PROTEIN T4-A), SQUAMOUS CELL CARCINOMA ANTIGEN 2 (SCCA-2), Ovarian carcinoma antigen CA125 (1A1-3B) (KIAA0049), MUCIN 1 (TUMOR-ASSOCIATED MUCIN), (CARCINOMA-ASSOCIATED MUCIN), (POLYMORPHIC EPITHELIAL MUCIN), (PEM), (PEMT), (EPISIALIN), (TUMOR-ASSOCIATED EPITHELIAL MEMBRANE ANTIGEN), (EMA), (H23AG), (PEANUT-REACTIVE URINARY MUCIN), (PUM), (BREAST CARCINOMA-ASSOCIATED ANTIGEN DF3), CTCL tumor antigen sel-1, CTCL tumor antigen se14-3, CTCL tumor antigen se20-4, CTCL tumor antigen se20-9, CTCL tumor antigen se33-1, CTCL tumor antigen se37-2, CTCL tumor antigen se57-1, CTCL tumor antigen se89-1, Prostate-specific membrane antigen, 5T4 oncofetal trophoblast glycoprotein, Orf73 Kaposi'"'"'s sarcoma-associated herpesvirus, MAGE-Cl (cancer/testis antigen CT7), MAGE-B1 ANTIGEN (MAGE-XP ANTIGEN) (DAM10), MAGE-B2 ANTIGEN (DAME), MAGE-2 ANTIGEN, MAGE-4a antigen, MAGE-4b antigen, Colon cancer antigen NY-CO-45, Lung cancer antigen NY-LU-12 variant A, Cancer associated surface antigen, Adenocarcinoma antigen ART1, Paraneoplastic associated brain-testis-cancer antigen (onconeuronal antigen MA2;

paraneoplastic neuronal antigen), Neuro-oncological ventral antigen 2 (NOVA2), Hepatocellular carcinoma antigen gene 520, TUMOR-ASSOCIATED ANTIGEN CO-029, Tumor-associated antigen MAGE-X2, Synovial sarcoma, X breakpoint 2, Squamous cell carcinoma antigen recognized by T cell, Serologically defined colon cancer antigen 1, Serologically defined breast cancer antigen NY-BR-15, Serologically defined breast cancer antigen NY-BR-16, Chromogranin A, parathyroid secretory protein 1, DUPAN-2, CA 19-9, CA 72-4, CA 195, or Carcinoembryonic antigen (CEA).

35. The device of claim 20, wherein the device is a needle, endoscopic manipulator, catheter, surgical implantation tool, or minimally invasive surgical device.

36. The device of claim 20, wherein the polymer matrix comprises polylactic acid, polyglycolic acid, polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA) polymer, alginate, alginate derivative, gelatin, collagen, fibrin, agarose, hyaluronic acid, natural polysaccharide, synthetic polysaccharide, polyamino acid, polyester, polyanhydride, polyphosphazine, poly(vinyl alcohol), poly(alkylene oxide), modified styrene polymer, pluronic polyol, polyoxamer, poly(uronic acid), poly(vinylpyrrolidone).

37. The device of claim 20, wherein the polymer matrix comprises poly(lactic-co-glycolic acid) (PLGA).