Antibody molecules to CD138 and uses thereof
Antibody molecules that specifically bind to CD138 are disclosed. The antibody molecules can be used to treat, prevent, and/or diagnose disorders, such as multiple myeloma.
1. An anti-CD138 antibody molecule comprising:
(a) a heavy chain variable region (VH), wherein the VH comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), wherein the VH comprises:
(i) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 350, 355, or 356, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 351, and an HCDR3 comprising the amino acid sequence of FVY; or
(ii) an HCDR1 comprising the amino acid sequence of SEQ ID NO: 380, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 381 or 382, and an HCDR3 comprising the amino acid sequence of FVY; and
(b) a light chain variable region (VL), wherein the VL comprises three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein the VL comprises:
an LCDR1 comprising the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that differs by 1 conservative amino acid substitution therefrom; an LCDR2 comprising the amino acid sequence of SEQ ID NO: 353; and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 354.
2. The antibody molecule of claim 1 , which is a synthetic antibody molecule, a humanized antibody molecule, or an isolated antibody molecule, and/or is a monovalent antibody molecule, a multivalent antibody molecule, a monospecific molecule, or a multispecific antibody molecule.
3. The antibody molecule of claim 1 , comprising a heavy chain constant region of IgG chosen from IgG1, IgG2, IgG3, or IgG4, and/or a light chain constant region of kappa or lambda light chain.
4. The antibody molecule of claim 1 , comprising an Fc region comprising one or more mutations that increases the binding affinity to neonatal receptor FcRn and/or the half-life of the antibody molecule.
5. An antibody-molecule drug conjugate (ADC) comprising an antibody molecule of claim 1 .
6. A pharmaceutical composition comprising an antibody molecule of claim 1 and a pharmaceutically acceptable carrier.
7. A nucleic acid molecule encoding a heavy chain variable region (VH), a light chain variable region (VL), or both, of an antibody molecule of claim 1 .
8. A vector comprising a nucleic acid molecule of claim 7 .
9. A cell comprising a nucleic acid molecule of claim 7 .
10. A kit comprising an antibody molecule of claim 1 and instructions to use of the antibody molecule or composition.
11. A container comprising an antibody molecule of claim 1 .
12. A method of producing an anti-CD138 antibody molecule, the method comprising culturing a cell of claim 9 under conditions that allow production of an antibody molecule, thereby producing the antibody molecule.
13. A method of causing an ADCC activity, the method comprising contacting a CD138-expressing cell or a subject comprising said cell with an antibody molecule of claim 1 , thereby causing the ADCC activity.
14. A method of treating a CD138-expressing cancer, the method comprising administering to a subject in need thereof an effective amount of an antibody molecule of claim 1 , thereby treating the CD138-expressing cancer.
15. The method of claim 14 , wherein the CD138-expressing cancer is a myeloma.
16. A method of treating a CD138-expressing precancerous condition, the method comprising administering to a subject in need thereof an effective amount of an antibody molecule of claim 1 , thereby treating the CD138-expressing precancerous condition.
17. The method of claim 16 , wherein the CD138-expressing precancerous condition is smoldering myeloma or monoclonal gammopathy of undetermined significance (MGUS).
18. A method of detecting a CD138 molecule, the method comprising contacting a cell or a subject with an antibody molecule of claim 1 , thereby detecting the CD138 molecule.
19. The antibody molecule of claim 1 , wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 350, 355, or 356, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 351, and an HCDR3 comprising the amino acid sequence of FVY.
20. The antibody molecule of claim 1 , wherein the VH comprises an HCDR1 comprising the amino acid sequence of SEQ ID NO: 380, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 381 or 382, and an HCDR3 comprising the amino acid sequence of FVY.
21. The antibody molecule of claim 1 , wherein:
(a) the VH comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 350, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 351, and an HCDR3 comprising the amino acid sequence of FVY; and
(b) the VL comprises: an LCDR1 comprising the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that differs by 1 conservative amino acid substitution therefrom, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 353, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 354.
22. The antibody molecule of claim 1 , wherein:
(a) the VH comprises: an HCDR1 comprising the amino acid sequence of SEQ ID NO: 355, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 351, and an HCDR3 comprising the amino acid sequence of FVY; and
(b) the VL comprises: an LCDR1 comprising the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that differs by 1 conservative amino acid substitution therefrom, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 353, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 354.
23. The antibody molecule of claim 1 , wherein:
(a) the VH comprises: an HCDR1 comprising an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 356, an HCDR2 comprising an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 351, and an HCDR3 comprising the amino acid sequence of FVY; and
(b) the VL comprises: an LCDR1 comprising the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that differs by 1 conservative amino acid substitution therefrom, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 353, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 354.
24. The antibody molecule of claim 1 , wherein:
(a) the VH comprises: an HCDR1 comprising an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 380, an HCDR2 comprising an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 381, and an HCDR3 comprising the amino acid sequence of FVY; and
(b) the VL comprises: an LCDR1 comprising the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that differs by 1 conservative amino acid substitution therefrom, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 353, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 354.
25. The antibody molecule of claim 1 , wherein:
(a) the VH comprises: an HCDR1 comprising an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 380, an HCDR2 comprising an amino acid sequence comprising the amino acid sequence of SEQ ID NO: 382, and an HCDR3 comprising the amino acid sequence of FVY; and
(b) the VL comprises: an LCDR1 comprising the amino acid sequence of SEQ ID NO: 352 or an amino acid sequence that differs by 1 conservative amino acid substitution therefrom, an LCDR2 comprising the amino acid sequence of SEQ ID NO: 353, and an LCDR3 comprising the amino acid sequence of SEQ ID NO: 354.
26. The antibody molecule of claim 1 , wherein the VH comprises an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of SEQ ID NO: 293, 294, 295, 296, or 297, and/or wherein the VL the VL comprises an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues from, or has at least 85, 90, 95, 99 or 100% homology with, the amino acid sequence of 292.
27. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 293, 294, 295, 296, or 297, or an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues therefrom, or has at least 85, 90, 95, 99 or 100% homology therewith.
28. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 293, 294, 295, 296, or 297.
29. The antibody molecule of claim 1 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 292, or an amino acid sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acid residues therefrom, or has at least 85, 90, 95, 99 or 100% homology therewith.
30. The antibody molecule of claim 1 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 292.
31. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 293, and wherein the VL comprises the amino acid sequence of 292.
32. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 294, and wherein the VL comprises the amino acid sequence of 292.
33. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 295, and wherein the VL comprises the amino acid sequence of 292.
34. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 296, and wherein the VL comprises the amino acid sequence of 292.
35. The antibody molecule of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 297, and wherein the VL comprises the amino acid sequence of 292.
36. The antibody molecule of claim 1 , comprising a heavy chain constant region of IgG1 and/or a light chain constant region of kappa light chain.
37. The antibody molecule of claim 1 , which is an afucosylated antibody molecule.