IP Library › Granted Patent US 9,937,249
Granted Patent B2
US 9,937,249 · App. 14/394,552 · Granted Apr 10, 2018

Mesoporous silica compositions for modulating immune responses

Inventors: Jaeyun Kim (Gyeonggi-do, KR); Weiwei Aileen Li (Cambridge, MA); David J. Mooney (Sudbury, MA)
Assignee: President and Fellows of Harvard College
A61K39/0011A61K9/0019A61K9/1611A61K38/18A61K38/193A61K39/39A61K2039/55522A61K2039/55555A61K2039/55561
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Quick Facts
Patent No.
US 9,937,249
App. No.
14/394,552
Granted
Apr 10, 2018
Kind
B2
Abstract

A composition comprising mesoporous silica rods comprising an immune cell recruitment compound and an immune cell activation compound, and optionally comprising an antigen such as a tumor lysate. The composition is used to elicit an immune response to a vaccine antigen.

Claims (46)

1. A composition comprising mesoporous silica rods comprising

an immune cell recruitment compound comprising granulocyte macrophage-colony stimulating factor (GM-CSF), chemokine (C-C motif) ligand 21 (CCL-21), chemokine (C-C motif) ligand 19 (CCl-19), or a FMS-like tyrosine kinase 3 (Flt-3) ligand; and

an immune cell activation compound comprising a TLR agonist,

wherein said rods comprise a length of 25 μm to 500 μm and pores of between 2 nm to 50 nm in diameter, and

wherein said rods are stacked into a 3D structure, wherein said structure comprises micro spaces that allow for immune cell infiltration or trafficking.

2. An injectable composition comprising mesoporous silica rods comprising

an immune cell recruitment compound comprising granulocyte macrophage-colony stimulating factor (GM-CSF), chemokine (C-C motif) ligand 21 (CCL-21), chemokine (C-C motif) ligand 19 (CCl-19), or a FMS-like tyrosine kinase 3 (Flt-3) ligand; and

an immune cell activation compound comprising a TLR agonist,

wherein said rods comprise a length of 25 μm to 500 μm and pores of between 2 nm to 50 nm in diameter, and

wherein said rods self-assemble into a 3D structure in vivo, and wherein said structure comprises micro spaces that allow for immune cell infiltration or trafficking.

3. The composition of claim 1 , wherein said TLR agonist comprises a pathogen associated molecular pattern (PAMP).

4. The composition of claim 3 , wherein said PAMP comprises a bacterially-derived immunomodulator.

5. The composition of claim 1 , wherein said TLR agonist comprises a nucleic acid, a lipid, double stranded deoxyribonucleic acid (DNA), double stranded ribonucleic acid (RNA), or a lipopolysaccharide.

6. The composition of claim 1 , wherein said TLR agonist comprises a TLR3 agonist or a TLR9 agonist.

7. The composition of claim 1 , wherein said rods comprise pores of between 2-50 nm in diameter.

8. The composition of claim 1 , wherein said rods comprise pores of between 5-25 nm in diameter.

9. The composition of claim 1 , wherein said rods comprise pores of between 5-10 nm in diameter.

10. The composition of claim 1 , wherein said rods comprise pores of approximately 8 nm in diameter.

11. The composition of claim 1 , wherein said rods comprise a length of 25 μm to 250 μm.

12. The composition of claim 1 , wherein said rods comprise a length of 80 μm to 120 μm.

13. The composition of claim 1 , wherein said recruitment compound comprises GM-CSF.

14. The composition of claim 1 , wherein said composition further comprises an antigen.

15. The composition of claim 14 , wherein said antigen comprises a tumor antigen.

16. The composition of claim 15 , wherein said tumor antigen is present in a tumor cell lysate.

17. The composition of claim 14 , wherein said antigen comprises MAGE-1, MART-1/melana, tyrosinase, ganglioside, gp100, GD-2, O-acetylated GD-3, GM-2, Mucin 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), 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, seriologically defined colon cancer antigen 1, seriologically defined breast cancer antigen NY-BR-15, seriologically 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).

18. The composition of claim 1 , wherein said rods comprise a length of 30 μm to 100 μm.

19. The composition of claim 1 , wherein said rods comprise a length of 50 μm to 250 μm.

20. The composition of claim 2 , wherein said TLR agonist comprises a pathogen associated molecular pattern (PAMP).

21. The composition of claim 20 , wherein said PAMP comprises a bacterially-derived immunomodulator.

22. The composition of claim 2 , wherein said TLR agonist comprises a nucleic acid, a lipid, double stranded deoxyribonucleic acid (DNA), double stranded ribonucleic acid (RNA), or a lipopolysaccharide.

23. The composition of claim 2 , wherein said TLR agonist comprises a TLR3 agonist or a TLR9 agonist.

24. The composition of claim 2 , wherein said rods comprise pores of between 2-50 nm in diameter.

25. The composition of claim 2 , wherein said rods comprise pores of between 5-25 nm in diameter.

26. The composition of claim 2 , wherein said rods comprise pores of between 5-10 nm in diameter.

27. The composition of claim 2 , wherein said rods comprise pores of approximately 8 nm in diameter.

28. The composition of claim 2 , wherein said rods comprise a length of 25 μm to 250 μm.

29. The composition of claim 2 , wherein said rods comprise a length of 80 μm to 120 μm.

30. The composition of claim 2 , wherein said recruitment compound comprises GM-CSF.

31. The composition of claim 2 , wherein said composition further comprises an antigen.

32. The composition of claim 31 , wherein said antigen comprises a tumor antigen.

33. The composition of claim 32 , wherein said tumor antigen is present in a tumor cell lysate.

34. The composition of claim 31 , wherein said antigen comprises MAGE-1, MART-1/melana, tyrosinase, ganglioside, gp100, GD-2, O-acetylated GD-3, GM-2, Mucin 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), 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, seriologically defined colon cancer antigen 1, seriologically defined breast cancer antigen NY-BR-15, seriologically 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 composition of claim 2 , wherein said rods comprise a length of 30 μm to 100 μm.

36. The composition of claim 2 , wherein said rods comprise a length of 50 μm to 250 μm.

37. The composition of claim 1 , wherein said rods comprise a diameter from 1.5 μm to 10 μm.

38. The composition of claim 2 , wherein said rods comprise a diameter from 1.5 μm to 10 μm.

Assignments (1)
CONFIRMATORY LICENSE Recorded Nov 13, 2014
From: HARVARD UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 034229/0862 →
Continuity (2)
Provisional Application 61624568 · Apr 16, 2012
Related Publication 20150072009A1 · Mar 12, 2015