Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy
The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.
1. A method of treating cancer, comprising administrating a composition to a subject in need thereof, wherein the composition comprises:
a cationic lipid comprising R-DOTAP; and
a T-cell, wherein the T-cell is antigen specific for the cancer being treated and wherein the antigen is a tumor-associated antigen
wherein the T-cell is a CD4+ T-cell, a CD8+ T-cell, an autologous T-cell or a combination thereof,
thereby treating cancer.
2. The composition of claim 1 , wherein the at least one T-cell comprise adoptively transferred T-cells.
3. A method of treating cancer by inducing the in vivo expansion of adoptively transferred T-cells, comprising administrating a composition to a subject in need thereof, wherein the composition comprises:
a cationic lipid comprising R-DOTAP, and
an adoptively transferred T-cell, wherein the adoptively transferred T-cell is antigen specific for the cancer being treated and wherein the antigen is a tumor-associated antigen,
thereby treating cancer.
4. The method of claim 3 where the adoptively transferred T-cell comprises an autologous T-cell.
5. The method of claim 3 where the adoptively transferred T-cell comprises a CD4+ T-cell.
6. The method of claim 3 where the adoptively transferred T-cell comprises a CD8+ T-cell.
7. A method of treating cancer, comprising administrating to a subject in need thereof:
a cationic lipid comprising R-DOTAP, and
a T-cell, wherein the T-cell is antigen specific for the cancer being treated, wherein the antigen is a tumor-associated antigen, wherein the T-cell is a CD4+ T-cell, a CD8+ T-cell, an autologous T-cell or a combination thereof, and
wherein the cationic lipid and the T cell are administered separately and concurrently,
thereby treating cancer.
8. The method of claim 7 , wherein the T-cell comprise adoptively transferred T-cells.
9. A method of treating cancer by inducing the in vivo expansion of adoptively transferred T-cells comprising administrating to a subject in need thereof:
a cationic lipid comprising R-DOTAP, and
an adoptively transferred T-cell, wherein the T-cell is antigen specific for the cancer being treated and wherein the antigen is a tumor-associated antigen,
wherein the cationic lipid and the adoptively transferred T-cell are administered separately and concurrently,
thereby treating cancer.
10. The method of claim 9 , where the adoptively transferred T-cell comprises an antigen specific adoptively transferred T-cell.
11. The method of claim 1 , wherein the tumor-associated antigen is an HPV antigen.
12. The method of claim 11 , wherein the HPV antigen is HPV16-E7.
13. The method of claim 3 , wherein the tumor-associated antigen is an HPV antigen.
14. The method of claim 13 , wherein the HPV antigen is HPV16-E7.
15. The method of claim 7 , wherein the tumor-associated antigen is an HPV antigen.
16. The method of claim 15 , wherein the HPV antigen is HPV16-E7.
17. The method of claim 9 , wherein the tumor-associated antigen is an HPV antigen.
18. The method of claim 11 , wherein the HPV antigen is HPV16-E7.