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 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 amino acid sequence of SEQ ID NO:4 or SEQ ED 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 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 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.
6. 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 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:8.
7. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof is a chimeric antibody or a fragment thereof.
8. The method of claim 3 , wherein the monoclonal antibody or a fragment thereof is a humanized antibody or a fragment thereof.
9. 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 disorder is human immunodeficiency virus infection or an autoimmune disease; and
wherein the antibody or a fragment thereof comprises a heavy chain variable region comprising 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 amino acid sequence of SEQ ID NO:4 or SEQ ID NO:8.
10. The method of claim 9 , wherein the disorder is human immunodeficiency virus infection.
11. 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 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 amino acid sequence of SEQ ID NO;4 or SEQ ID NO:8.