Phage conjugates and uses thereof
The present invention relates to pharmaceutical compositions containing lipid-bacteriophage conjugates, wherein the bacteriophage:lipid ratio is in the range of 3:1 to 100:1 and wherein the lipid is an immunologically active lipid and the bacteriophage is a filamentous bacteriophage, and uses thereof. Preferably, the bacteriophage is engineered to stimulate an immune response and/or bind to a target cell.
1. A pharmaceutical composition comprising lipid-bacteriophage conjugates, wherein the bacteriophage is conjugated to at least one lipid by means of a non-covalent bond and the bacteriophage lipid ratio is between 3:1 and 100:1; wherein the lipid is selected from the group consisting of alpha-galactosylceramide (aGalCer), glycosphingolipids, palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC), monophosphoryl lipid A and their natural or synthetic analogues and the bacteriophage is a filamentous bacteriophage.
2. The pharmaceutical composition according to claim 1 wherein the immunologically active lipid is aGalCer.
3. The pharmaceutical composition according to claim 1 wherein the bacteriophage is a filamentous bacteriophage engineered to express an exogenous sequence or a fragment thereof, and said exogenous sequence or a fragment thereof stimulates an immune response and/or selectively binds to a cell surface molecule on a target cell.
4. The pharmaceutical composition according to claim 3 , wherein the exogenous sequence or a fragment thereof is encoded by a nucleic acid fused to a nucleotide sequence encoding a coat protein of the bacteriophage.
5. The pharmaceutical composition according to claim 4 , wherein the exogenous sequence encodes a protein or a fragment thereof, an antibody or a fragment thereof, or a chemokine.
6. The pharmaceutical composition according to claim 5 , wherein the protein is ovalbumin, the antibody or antibody fragment is a single chain antibody fragment (scFv) directed against the DEC 205 receptor comprising a variable region of a light chain having an amino acid sequence of SEQ ID NO: 3 and a variable region of a heavy chain having an amino acid sequence of SEQ ID NO: 5 and the chemokine is XCL1.
7. The pharmaceutical composition according to claim 4 , wherein the coat protein is the protein pIII or the protein pVIII.
8. The pharmaceutical composition according to claim 4 , wherein the coat protein has an amino acid sequence selected from the group consisting of: SEQ ID NO: 13, SEQ ID NO: 15 and SEQ ID NO: 17.
9. The pharmaceutical composition according to claim 3 , wherein the target cell is a dendritic cell.
10. The pharmaceutical composition according to claim 1 wherein the bacteriophage is linked to a combination of lipids.
11. The pharmaceutical composition according to claim 1 , wherein the filamentous bacteriophage is selected from the group consisting of: m13, fd and f1.
12. The pharmaceutical composition according to claim 1 further comprising pharmaceutically acceptable excipients, vehicles or diluents.
13. A method for the treatment of an infection or an hyperproliferative disease, comprising administering a pharmaceutical composition of claim 1 to a subject in need thereof.
14. The method according to claim 13 wherein the hyperproliferative disease is a tumour.
15. The pharmaceutical composition according to claim 9 , wherein said dendritric cell is a myeloid dendritric cell type I or type II, or a plasmacytoid dendritic cell.
16. The method of claim 14 , wherein the tumour is a melanoma.