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 . An immunotherapy composition comprising at least one cationic lipid and at least one type of T-cell, wherein the at least one cationic lipid and at least one type of T-cell may be administered in combination or separately.
2 . The composition of claim 1 where the T-cell comprises an antigen specific T-cell.
3 . The composition of claim 1 where the T-cell comprises an adoptively transferred T-cell.
4 . The composition of claim 1 where the T-cell comprises an autologous T-cell.
5 . The composition of claim 1 where the T-cell comprises a CD4 + T-cell.
6 . The composition of claim 1 where the T-cell comprises a CD8 + T-cell.
7 . The composition of claim 1 where the cationic lipid comprises DOTAP, DDA, DOTMA or DOEPC, and combinations thereof.
8 . A method of treating or preventing a disease, comprising the administration of a composition to a subject in need thereof, wherein the composition comprises at least one cationic lipid and at least one type of T-cell, wherein the at least one cationic lipid and at least one type of T-cell may be administered in combination or separately.
9 . The composition of claim 8 , wherein the T-cells comprise adoptively transferred T-cells.
10 . The method of claim 8 , resulting in the priming and boosting of the adoptively transferred T-cells.
11 . The method of claim 8 , where the disease comprises cancer.
12 . The method of claim 8 , where the disease comprises an infectious disease.
13 . The method of claim 8 , where the T-cell comprises a CD4 + T-cell.
14 . The method of claim 8 , where the T-cell comprises a CD8 + T-cell.
15 . The method of claim 8 where the T-cell comprises an autologous T-cell.
16 . The method of claim 8 where the cationic lipid comprises DOTAP, DDA, DOTMA or DOEPC, and combinations thereof.
17 . A method of treating or preventing a disease by inducing the in vivo expansion of adoptively transferred T-cells, comprising the administration of a composition to a subject in need thereof, wherein the composition comprises at least one cationic lipid and at least one type of adoptively transferred T-cell, wherein the at least one cationic lipid and at least one type of adoptively transferred T-cell may be administered in combination or separately.
18 . The method of claim 17 where the T-cell comprises an antigen specific T-cell.
19 . The method of claim 17 where the T-cell comprises an autologous T-cell.
20 . The method of claim 17 where the T-cell comprises a CD4 + T-cell.
21 . The method of claim 17 where the T-cell comprises a CD8 + T-cell.
22 . The method of claim 17 where the cationic lipid comprises DOTAP, DDA, DOTMA or DOEPC, and combinations thereof.