Adoptive cell therapy using spherical nucleic acids (SNAs)
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 method of treating lung cancer or melanoma in an individual comprising administering to the individual a composition comprising a pharmaceutically acceptable carrier and a T cell having a spherical nucleic acid (SNA) contained therein, wherein the T cell is obtained from an individual and the SNA comprises a nanoparticle, an immunostimulatory oligonucleotide comprising a sequence that is a toll-like receptor (TLR) agonist on the surface of the nanoparticle, and a tumor associated antigen.
2. A method of producing an immune response to lung cancer or melanoma in an individual, comprising administering to the individual an effective amount of a composition comprising a pharmaceutically acceptable carrier and a T cell having a spherical nucleic acid (SNA) contained therein, wherein the T cell is obtained from an individual and the SNA comprises a nanoparticle, an immunostimulatory oligonucleotide comprising a sequence that is a toll-like receptor (TLR) agonist on the surface of the nanoparticle, and a tumor associated antigen, thereby producing an immune response to cancer in the individual.
3. The method of claim 1 , wherein the nanoparticle is a liposome.
4. The method of claim 1 , wherein the oligonucleotide comprises RNA or DNA.
5. The method of claim 1 , wherein the oligonucleotide comprises a CpG nucleotide sequence.
6. The method of claim 1 , wherein the nanoparticle has a diameter of 50 nanometers or less.
7. The method of claim 1 , wherein the composition comprising about 10 to about 80 double stranded oligonucleotides.
8. The method of claim 1 , wherein the tumor associated antigen is encapsulated in the nanoparticle, or wherein the tumor associated antigen is on the surface of the nanoparticle.
9. The method of claim 1 , wherein the composition further comprises an additional oligonucleotide.
10. The method of claim 9 , wherein the additional oligonucleotide comprises RNA or DNA.
11. The method of claim 10 , wherein the additional oligonucleotide is capable of hybridizing to a polynucleotide encoding a gene and the additional oligonucleotide is complementary to all or a portion of the polynucleotide, wherein hybridizing between the polynucleotide and the oligonucleotide occurs over a length of the polynucleotide with a degree of complementarity sufficient to inhibit expression of the gene product.
12. The method of claim 11 , wherein the RNA is an inhibitory RNA (RNAi).
13. The method of claim 12 , 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.
14. The method of claim 11 , wherein the RNA is a microRNA.
15. The method of claim 11 , wherein the DNA is an anti-sense DNA.
16. The method of claim 11 , wherein expression of the gene product is inhibited in vivo, or wherein expression of the gene product is inhibited in vitro.
17. The method of claim 11 , wherein the gene is programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1).
18. The method of claim 2 , wherein the nanoparticle is a liposome.
19. The method of claim 2 , wherein the oligonucleotide comprises RNA or DNA.
20. The method of claim 2 , wherein the oligonucleotide comprises a CpG nucleotide sequence.
21. The method of claim 2 , wherein the nanoparticle has a diameter of 50 nanometers or less.
22. The method of claim 2 , wherein the composition comprising about 10 to about 80 double stranded oligonucleotides.
23. The method of claim 2 , wherein the tumor associated antigen is encapsulated in the nanoparticle, or wherein the tumor associated antigen is on the surface of the nanoparticle.
24. The method of claim 2 , wherein the composition further comprises an additional oligonucleotide.
25. The method of claim 24 , wherein the additional oligonucleotide comprises RNA or DNA.
26. The method of claim 25 , wherein the additional oligonucleotide is capable of hybridizing to a polynucleotide encoding a gene and the additional oligonucleotide is complementary to all or a portion of the polynucleotide, wherein hybridizing between the polynucleotide and the oligonucleotide occurs over a length of the polynucleotide with a degree of complementarity sufficient to inhibit expression of the gene product.
27. The method of claim 26 , wherein the RNA is an inhibitory RNA (RNAi).
28. The method of claim 27 , 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.
29. The method of claim 26 , wherein the RNA is a microRNA.
30. The method of claim 26 , wherein the DNA is an anti-sense DNA.
31. The method of claim 26 , wherein expression of the gene product is inhibited in vivo, or wherein expression of the gene product is inhibited in vitro.
32. The method of claim 26 , wherein the gene is programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1).