ILT7 binding molecules and methods of using the same
The present invention is directed to ILT7 binding molecules, e.g., anti-ILT7 antibodies, and methods for treating or preventing conditions and diseases associated with ILT7-expressing cells such as autoimmune diseases.
1. A method of treating a disease associated with ILT7-expressing cells that comprises inflammation, the method comprising administering an effective amount of an anti-Immunoglobulin-like transcript-7 (ILT7) antibody to a subject in need thereof, wherein the ILT7 antibody comprises Complementarity-Determining Regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 203, 204, 205, 208, 209, and 210, respectively, and wherein the administering is effective in treating the disease as determined by detecting a reduced level of interferon-alpha or plasmacytoid dendritic cells (pDCs) in the subject in need thereof after the administering.
2. The method of claim 1 , wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 consist of the amino acid sequences of 203, 204, 205, 208, 209, and 210, respectively.
3. The method of claim 1 , wherein the ILT7 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH and VL regions comprise an amino acid sequence at least 95% identical to SEQ ID NO:202 and SEQ ID NO:207, respectively.
4. The method of claim 3 , wherein the VH and VL regions consist of the amino acid sequence of SEQ ID NO:202 and SEQ ID NO:207, respectively.
5. The method of claim 3 , wherein the ILT7 antibody comprises a heavy chain immunoglobulin constant domain selected from the group consisting of: an IgA constant domain, an IgE constant domain, an IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, an IgG4 constant domain, and an IgM constant domain.
6. The method of claim 5 , wherein the antibody comprises the IgG1 constant domain.
7. The method of claim 3 , wherein the ILT7 antibody comprises a light chain immunoglobulin constant domain selected from the group consisting of: an Ig kappa constant domain and an Ig lambda constant domain.
8. The method of claim 7 , wherein the ILT7 antibody comprises the lambda constant domain.
9. The method of claim 1 , wherein the ILT7 antibody is a monoclonal antibody.
10. The method of claim 1 , wherein the ILT7 antibody is a human, a chimeric, a humanized, or a resurfaced antibody.
11. The method of claim 1 , comprising evaluating the subject in need thereof, or a sample obtained therefrom, via a test selected from the group consisting of: magnetic resonance imaging (MRI) scan, x-radiographic imaging, computed tomographic (CT) scan, flow cytometry or fluorescence-activated cell sorter (FACS) analysis, histology, gross pathology, and blood chemistry.
12. The method of claim 1 , comprising detecting the reduced level of pDCs, wherein the level is reduced by at least about 1-fold as compared to an otherwise comparable method lacking the administering.
13. The method of claim 1 , comprising detecting the reduced level of interferon-alpha, wherein the level is reduced by at least about 1-fold as compared to an otherwise comparable method lacking the administering.
14. The method of claim 1 , wherein the subject in need thereof is human.
15. The method of claim 1 , wherein the subject in need thereof is a primate.
16. The method of claim 1 , wherein the antibody is afucosylated.
17. The method of claim 1 , wherein the administering is by infusion.
18. The method of claim 1 , wherein the administering is repeated.
19. The method of claim 18 , wherein the administering that is repeated comprises 5 administrations of the ILT7 antibody.
20. The method of claim 1 , wherein the subject achieves a complete response for at least one month following the administering.
21. The method of claim 1 , wherein the disease associated with ILT7-expressing cells that comprises inflammation is an autoimmune disease.
22. A method of reducing the level of interferon-alpha or plasmacytoid dendritic cells (pDCs), the method comprising administering an effective amount of an anti-ILT7 antibody to a primate subject in need thereof, wherein the ILT7 antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), and wherein the VH and VL regions comprise an amino acid sequence comprising SEQ ID NO:202 and SEQ ID NO:207, respectively.