Creating bioengineered lymph nodes
View Patent ↗The invention provides compositions and methods of treating various conditions, including tumors, with compositions comprising dendritic cells expressing exogenous chemokines.
1. A composition comprising an isolated, engineered dendritic cell comprising exogenous cDNAs encoding exogenous Chemokine (C—C Motif) Ligand (CCL) 8 (CCL-8), CCL-18, and C—X—C Motif Chemokine 13 (CXCL-13).
2. The composition of claim 1 , wherein the engineered dendritic cell is selected from the group consisting of a CD14 + blood monocyte-derived dendritic cell, a dermal or interstitial dendritic cell, a Langerhans cell, and a plasmacytoid dendritic cell.
3. The composition of claim 1 , wherein the engineered dendritic cell further comprises exogenous cDNA encoding at least one exogenous chemokine selected from the group consisting of CCL-1, CCL-2, CCL-3, CCL-4, CCL-5, CCL-13, CCL-17, CCL-20, CCL-21, CXCL-9, CXCL-10, CXCL-11, CXCL-14, CXCL-16, and Chemokine (C motif) ligand (XCL1).
4. The composition of claim 1 , wherein the dendritic cell is antigen-loaded.
5. The composition of claim 4 , wherein the antigen is selected from the group consisting of tumor, viral, bacterial, and fungal antigens.
6. The composition of claim 1 , wherein the dendritic cell expresses the exogenous CCL-8, CCL-18, and CXCL-13.
7. An isolated, engineered dendritic cell comprising exogenous cDNAs encoding exogenous CCL-8, CCL-18, and CXCL-13.
8. The engineered dendritic cell of claim 7 , wherein the dendritic cell further comprises exogenous cDNA encoding at least one exogenous chemokine selected from the group consisting of CCL-1, CCL-2, CCL-3, CCL-4, CCL-5, CCL-13, CCL-17, CCL-20, CCL-21, CXCL-9, CXCL-10, CXCL-11, CXCL-14, CXCL-16, and XCL1.
9. The engineered dendritic cell of claim 7 , wherein the dendritic cell is selected from the group consisting of a CD14 + blood monocyte-derived dendritic cell, a dermal or interstitial dendritic cell, a Langerhans cell, and a plasmacytoid dendritic cell.
10. The engineered dendritic cell of claim 7 , wherein the dendritic cell is antigen-loaded.
11. The engineered dendritic cell of claim 10 , wherein the antigen is selected from the group consisting of tumor, viral, bacterial, and fungal antigens.
12. The engineered dendritic cell of claim 7 , wherein the dendritic cell expresses the exogenous CCL-8, CCL-18, and CXCL-13.
13. A composition comprising an isolated, engineered dendritic cell transduced with plasmids, cosmids, or viral vectors encoding exogenous CCL-8, CCL-18, and CXCL-13.
14. The composition of claim 13 , wherein the engineered dendritic cell is selected from the group consisting of a CD14 + blood monocyte-derived dendritic cell, a dermal or interstitial dendritic cell, a Langerhans cell, and a plasmacytoid dendritic cell.
15. The composition of claim 13 , wherein the engineered dendritic cell is further transduced with vectors encoding at least one exogenous chemokine selected from the group consisting of CCL-1, CCL-2, CCL-3, CCL-4, CCL-5, CCL-13, CCL-17, CCL-20, CCL-21, CXCL-9, CXCL-10, CXCL-11, CXCL-14, CXCL-16, and Chemokine (C motif) ligand (XCL1).
16. The composition of claim 13 , wherein the engineered dendritic cell is antigen-loaded.
17. The composition of claim 16 , wherein the antigen is selected from the group consisting of tumor, viral, bacterial, and fungal antigens.
18. The composition of claim 13 , wherein the engineered dendritic cell expresses the exogenous CCL-8, CCL-18, and CXCL-13.
19. The composition of claim 13 , wherein the vectors are replication defective retroviruses, adenoviruses, or adeno-associated viruses.
20. An isolated engineered dendritic cell transduced with plasmids, cosmids, or viral vectors encoding exogenous CCL-8, CCL-18, and CXCL-13.
21. The engineered dendritic cell of claim 20 , wherein the dendritic cell is further transduced with vectors encoding at least one exogenous chemokine selected from the group consisting of CCL-1, CCL-2, CCL-3, CCL-4, CCL-5, CCL-13, CCL-17, CCL-20, CCL-21, CXCL-9, CXCL-10, CXCL-11, CXCL-14, CXCL-16, and XCL1.
22. The engineered dendritic cell of claim 20 , wherein the dendritic cell is selected from the group consisting of a CD14 + blood monocyte-derived dendritic cell, a dermal or interstitial dendritic cell, a Langerhans cell, and a plasmacytoid dendritic cell.
23. The engineered dendritic cell of claim 20 , wherein the dendritic cell is antigen-loaded.
24. The engineered dendritic cell of claim 23 , wherein the antigen is selected from the group consisting of tumor, viral, bacterial, and fungal antigens.
25. The engineered dendritic cell of claim 20 , wherein the dendritic cell expresses the exogenous CCL-8, CCL-18, and CXCL-13.
26. The engineered dendritic cell of claim 20 , wherein the vectors are replication defective retroviruses, adenoviruses, or adeno-associated viruses.