Mesoporous silica compositions comprising inflammatory cytokines for modulating immune responses

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.

1 .- 18 . (canceled) 
     
     
         19 . A method of inducing a systemic antigen-specific immune response to a vaccine antigen, comprising administering to a subject a composition comprising:
 mesoporous silica rods, wherein the mesoporous silica rods have a length of between 5 μm to 500 μm, and wherein the mesoporous silica rods comprise pores of between 2-50 nm in diameter; and   an inflammatory cytokine that recruits an immune cell to the mesoporous silica rods,   wherein the inflammatory cytokine is loaded into the mesoporous silica rods and is released from the mesoporous silica rods upon administration to a subject, and   wherein the mesoporous silica rods are capable of self-assembly in vivo into a three-dimensional scaffold that allows for immune cell infiltration.   
     
     
         20 . A method of inducing homing of vaccine antigen-specific immune cells to a lymph node, comprising administering to a subject a composition comprising:
 mesoporous silica rods, wherein the mesoporous silica rods have a length of between 5 μm to 500 μm, and wherein the mesoporous silica rods comprise pores of between 2-50 nm in diameter; and   an inflammatory cytokine that recruits an immune cell to the mesoporous silica rods,   wherein the inflammatory cytokine is loaded into the mesoporous silica rods and is released from the mesoporous silica rods upon administration to a subject, and   wherein the mesoporous silica rods are capable of self-assembly in vivo into a three-dimensional scaffold that allows for immune cell infiltration.   
     
     
         21 . The method of  claim 19 , wherein the mesoporous silica rods comprise pores of between 5-25 nm in diameter. 
     
     
         22 . The method of  claim 19 , wherein the mesoporous silica rods comprise pores of between 5-10 nm in diameter. 
     
     
         23 . The method of  claim 19 , wherein the mesoporous silica rods comprise pores of approximately 8 nm in diameter. 
     
     
         24 . The method of  claim 19 , wherein the mesoporous silica rods have a length of 5 μm to 25 μm. 
     
     
         25 . The method of  claim 19 , wherein the mesoporous silica rods have a length of 80 μm to 120 μm. 
     
     
         26 . The method of  claim 19 , wherein the inflammatory cytokine comprises 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. 
     
     
         27 . The method of  claim 19 , wherein the inflammatory cytokine comprises GM-CSF. 
     
     
         28 . The method of  claim 19 , wherein the composition further comprises a vaccine antigen. 
     
     
         29 . The method of  claim 28 , wherein the vaccine antigen comprises a tumor antigen. 
     
     
         30 . The method of  claim 29 , wherein the tumor antigen is selected from the group consisting of 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, and carcinoembryonic antigen (CEA). 
     
     
         31 . The method of  claim 19 , wherein the composition further comprises an immune cell activation compound. 
     
     
         32 . The method of  claim 31 , wherein the immune cell activation compound comprises a TLR agonist. 
     
     
         33 . The method of  claim 32 , wherein the TLR agonist comprises CpG ODN. 
     
     
         34 . The composition of  claim 19 , wherein the composition comprises an immune cell activation compound and an antigen. 
     
     
         35 . The composition of  claim 34 , wherein the inflammatory cytokine comprises GM-CSF, the immune cell activation compound comprises CpG-ODN, and the antigen comprises a tumor antigen. 
     
     
         36 . The method of  claim 19 , wherein the mesoporous silica rods are modified with a chemical group or a compound selected from the group consisting of an amine group, thiol group, chloro group, phosphonate group, glycolic acid, and lactic acid. 
     
     
         37 . The method of  claim 19 , wherein the subject is a human. 
     
     
         38 . The method of  claim 19 , wherein the composition is administered by injection.