Adoptive cell therapy using spherical nucleic acids (snas)

Abstract

The disclosure is related to compositions comprising a cell and a spherical nucleic acid (SNA) comprising a nanoparticle, an oligonucleotide on the surface of the nanoparticle, and an antigen; and to methods for production of such compositions and their applications, including but not limited to adoptive cell therapy.

1 . A composition comprising a pharmaceutically acceptable carrier and a cell having a spherical nucleic acid (SNA) contained therein, wherein the cell is obtained from an individual and the SNA comprises a nanoparticle, an oligonucleotide on the surface of the nanoparticle, and an antigen. 
     
     
         2 . The composition of  claim 1 , wherein the antigen is a prostate-specific antigen (PSA) peptide, mesothelin, glycoprotein 100 (gp100), prostate specific membrane antigen (PSMA), or prostatic acid phosphatase (PAP). 
     
     
         3 . The composition of  claim 1 , wherein the nanoparticle is a liposome. 
     
     
         4 . The composition of  claim 3 , wherein the liposome comprises a lipid selected from the group consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dimyristoyl-sn-phosphatidylcholine (DMPC), 1-palmitoyl-2-oleoyl-sn-phosphatidylcholine (POPC), 1,2-distearoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DSPG), 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DPPE), cardiolipin, and lipid A. 
     
     
         5 . The composition of  claim 3 , wherein the oligonucleotide comprises a tocopherol, a cholesterol moiety, DOPE-butamide-phenylmaleimido, or lyso-phosphoethanolamine-butamide-pneylmaleimido. 
     
     
         6 . The composition of  claim 1 , wherein the oligonucleotide comprises RNA or DNA. 
     
     
         7 . The composition of  claim 1 , wherein the oligonucleotide comprises a sequence that is a toll-like receptor (TLR) agonist. 
     
     
         8 . The composition of  claim 7 , wherein the TLR is chosen from the group consisting of toll-like receptor 1 (TLR1), toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), toll-like receptor 5 (TLR5), toll-like receptor 6 (TLR6), toll-like receptor 7 (TLR7), toll-like receptor 8 (TLR8), toll-like receptor 9 (TLR9), toll-like receptor 10 (TLR10), toll-like receptor 11 (TLR11), toll-like receptor 12 (TLR12), and toll-like receptor 13 (TLR13). 
     
     
         9 . The composition of  claim 1 , wherein the oligonucleotide comprises a CpG nucleotide sequence. 
     
     
         10 . The composition of  claim 1 , further comprising an additional oligonucleotide. 
     
     
         11 . The composition of  claim 10 , wherein the additional oligonucleotide comprises RNA or DNA. 
     
     
         12 . The composition of  claim 11 , wherein the RNA is a non-coding RNA. 
     
     
         13 . The composition of  claim 12 , wherein the non-coding RNA is an inhibitory RNA (RNAi). 
     
     
         14 . The composition of  claim 13 , wherein the RNAi is selected from the group consisting of a small inhibitory RNA (siRNA), a single-stranded RNA (ssRNA) that forms a triplex with double stranded DNA, and a ribozyme. 
     
     
         15 . The composition of  claim 12 , wherein the RNA is a microRNA. 
     
     
         16 . The composition of  claim 11 , wherein the DNA is antisense-DNA. 
     
     
         17 . The composition of  claim 1 , wherein the nanoparticle has a diameter of 50 nanometers or less. 
     
     
         18 . The composition of  claim 1  comprising about 10 to about 80 double stranded oligonucleotides. 
     
     
         19 . The composition of  claim 18  comprising 70 double stranded oligonucleotides. 
     
     
         20 . The composition of  claim 1 , wherein the cell is a T-cell, a natural killer (NK) cell, a B-cell, a macrophage, a dendritic cell, or a combination thereof. 
     
     
         21 . The composition of  claim 1 , wherein the antigen is encapsulated in the nanoparticle. 
     
     
         22 . The composition of  claim 1 , wherein the antigen is on the surface of the nanoparticle. 
     
     
         23 . (canceled) 
     
     
         24 . (canceled) 
     
     
         25 . A vaccine comprising the composition of  claim 1 , and an adjuvant. 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . (canceled)