Scaffolds for cell transplantation

Patent metadata

Field	Value
Publication number	US-9446107-B2
Application number	US-201514750423-A
Country	US
Kind code	B2
Filing date	Jun 25, 2015
Priority date	Dec 13, 2005
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

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.

First claim

What is claimed is:

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.

2. The device of claim 1 , wherein said device further comprises an extracellular matrix (ECM) component.

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

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

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

6. 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.

7. The device of claim 1 , wherein said scaffold composition comprises pores of greater than 100 μm in size.

8. The device of claim 7 , wherein the scaffold composition comprises pores of 400-500 μm in size.

9. 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.

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

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

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

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

14. The device of claim 1 , wherein the tumor antigen comprises a MAGE series of antigens, MART-1/melana, Tyrosinase, ganglioside, gp100, GD-2, O-acetylated GD-3, GM-2, MUC-1, Sos1, 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 se1-1, 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-C1 (cancer/testis antigen CT7), MAGE-B1 ANTIGEN (MAGE-XP ANTIGEN) (DAM10), MAGE-B2 ANTIGEN (DAM6), 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).

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

16. 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).

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

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

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

Assignees

• Harvard College
• Univ Michigan

Inventors

• Mooney David J
• Ali Omar Abdel-Rahman
• Barros E Silva Eduardo Alexandre
• Kong Hyun Joon
• Hill Jr Elliot Earl
• Boontheekul Tanyarut

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L2300/426

  Immunomodulating agents, i.e. cytokines, interleukins, interferons · CPC title

• A61L2430/30

  for muscle reconstruction · CPC title