Depletion of plasmacytoid dendritic cells
View Patent ↗The present invention relates to antibodies targeted to BDCA2 that deplete plasmacytoid dendritic cells (pDC) and methods of using the antibodies to treat disorders associated with pDC.
1. A method of depleting plasmacytoid dendritic cells (pDC) in a subject, comprising delivering to the subject an effective amount of an antibody or a fragment thereof that specifically binds to blood dendritic cell antigen-2 (BDCA2) and depletes pDC, thereby depleting pDC;
wherein the antibody or a fragment thereof comprises a heavy chain variable region comprising the three complementarity determining regions of the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:6; and/or
the antibody or a fragment thereof comprises a light chain variable region comprising the three complementarity determining regions of the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:8.
2. The method of claim 1 , wherein the BDCA2 is human BDCA2.
3. The method of claim 1 , wherein the antibody or a fragment thereof is a monoclonal antibody or a fragment or derivative thereof.
4. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof specifically binds the epitope IQNLKRNSSYFLGLSDPGGR (SEQ ID NO:9) or a fragment thereof of at least 5 contiguous amino acids.
5. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:2 or a sequence at least 90% identical thereto.
6. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:4 or a sequence at least 90% identical thereto.
7. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:6 or a sequence at least 90% identical thereto.
8. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:8 or a sequence at least 90% identical thereto.
9. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof is a chimeric antibody or a fragment thereof.
10. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof is a humanized antibody or a fragment thereof.
11. A method of treating a disorder associated with pDC in a subject in need thereof, comprising delivering to the subject a therapeutically effective amount an antibody or a fragment thereof that specifically binds to BDCA2 and depletes pDC, thereby treating the disorder;
wherein the antibody or a fragment thereof comprises a heavy chain variable region comprising the three complementarity determining regions of the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:6; and/or
the antibody or a fragment thereof comprises a light chain variable region comprising the three complementarity determining regions of the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:8.
12. The method of claim 11 , wherein the disorder is human immunodeficiency virus infection.
13. The method of claim 11 , wherein the disorder is an autoimmune disease.
14. The method of claim 11 , wherein the disorder is a cancer.
15. The method of claim 11 , wherein the disorder is pDC-derived leukemia.
16. The method of claim 11 , wherein the disorder is a disorder associated with tissue accumulation of pDC.
17. A method of depleting pDC in a mixed population of cells, comprising delivering to the mixed population of cells an effective amount of an antibody or a fragment thereof that specifically binds to BDCA2 and depletes pDC, thereby depleting pDC in the mixed population of cells;
wherein the antibody or a fragment thereof comprises a heavy chain variable region comprising the three complementarity determining regions of the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:6; and/or
the antibody or a fragment thereof comprises a light chain variable region comprising the three complementarity determining regions of the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:8.