Antibodies and pharmaceutical compositions thereof which bind urokinase-type plasminogen activator receptor (uPAR)
The present disclosure relates to binding agents (e.g. antibodies) that bind to and/or modulate the activity of a urokinase plasminogen activator receptor (uPAR/CD87), compositions comprising the antibodies, and methods involving use of the antibodies or compositions.
1. An isolated antibody or antigen-binding fragment thereof that specifically binds urokinase-type plasminogen activator receptor (uPAR), wherein said antibody or antigen-binding fragment competes for binding to uPAR with an antibody or antigen-binding fragment that comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO:40;
a VH CDR2 comprising the amino acid sequence of SEQ ID NO:42;
a VH CDR3 comprising the amino acid sequence of SEQ ID NO:44;
a VL CDR1 comprising the amino acid sequence of SEQ ID NO:34;
a VL CDR2 comprising the amino acid sequence of SEQ ID NO:36; and
a VL CDR3 comprising the amino acid sequence of SEQ ID NO:38.
2. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody or antigen-binding fragment comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO:40;
a VH CDR2 comprising the amino acid sequence of SEQ ID NO:42;
a VH CDR3 comprising the amino acid sequence of SEQ ID NO:44;
a VL CDR1 comprising the amino acid sequence of SEQ ID NO:34;
a VL CDR2 comprising the amino acid sequence of SEQ ID NO:36; and
a VL CDR3 comprising the amino acid sequence of SEQ ID NO:38.
3. The isolated antibody or antigen-binding fragment of claim 2 comprising:
a) a heavy chain comprising an amino acid sequence having at least 85% amino acid sequence identity to the full length V H of 2G10 (SEQ ID NO:16); and
b) a light chain comprising an amino acid sequence having at least 85% amino acid sequence identity to the full length V L of 2G10 (SEQ ID NO:17).
4. The antibody or antigen-binding fragment of claim 1 , wherein said antibody or antigen-binding fragment competes for binding to uPAR with an antibody from clone 2G10.
5. The isolated antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment is conjugated to a moiety selected from the group consisting of: a cytotoxic molecule, a detectable label, a fluorophore, a dye, a radioisotope, an enzyme, a peptide, a polypeptide, and a nucleic acid.
6. A pharmaceutical composition comprising:
the isolated antibody or antigen-binding fragment of claim 1 ; and
a pharmaceutically acceptable excipient.
7. The pharmaceutical composition of claim 6 , wherein the isolated antibody or antigen-binding fragment comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO:40;
a VH CDR2 comprising the amino acid sequence of SEQ ID NO:42;
a VH CDR3 comprising the amino acid sequence of SEQ ID NO:44;
a VL CDR1 comprising the amino acid sequence of SEQ ID NO:34;
a VL CDR2 comprising the amino acid sequence of SEQ ID NO:36; and
a VL CDR3 comprising the amino acid sequence of SEQ ID NO:38.
8. The pharmaceutical composition of claim 7 , wherein the isolated antibody or antigen-binding fragment comprises:
a) a heavy chain comprising an amino acid sequence having at least 85% amino acid sequence identity to the full length V H of 2G10 (SEQ ID NO:16); and
b) a light chain comprising an amino acid sequence having at least 85% amino acid sequence identity to the full length V L of 2G10 (SEQ ID NO:17).
9. The pharmaceutical composition of claim 6 , wherein the composition further comprises an antibody or antigen-binding fragment thereof that competes with an integrin for binding to uPAR, wherein the antibody or antigen-binding fragment that competes with an integrin for binding to uPAR comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO:39;
a VH CDR2 comprising the amino acid sequence of SEQ ID NO:41;
a VH CDR3 comprising the amino acid sequence of SEQ ID NO:43;
a VL CDR1 comprising the amino acid sequence of SEQ ID NO:33;
a VL CDR2 comprising the amino acid sequence of SEQ ID NO:35; and
a VL CDR3 comprising the amino acid sequence of SEQ ID NO:37.
10. The pharmaceutical composition of claim 9 , wherein the integrin is a β1 integrin.
11. The pharmaceutical composition of claim 10 , wherein the β1 integrin is a α5β1 or α3β1.
12. A kit comprising:
the isolated antibody or antigen-binding fragment of claim 1 conjugated to a detectable label; and
instructions for using the isolated antibody or antigen-binding fragment to detect uPAR expressing cells.
13. The kit of claim 12 , wherein the isolated antibody or antigen-binding fragment comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO:40;
a VH CDR2 comprising the amino acid sequence of SEQ ID NO:42;
a VH CDR3 comprising the amino acid sequence of SEQ ID NO:44;
a VL CDR1 comprising the amino acid sequence of SEQ ID NO:34;
a VL CDR2 comprising the amino acid sequence of SEQ ID NO:36; and
a VL CDR3 comprising the amino acid sequence of SEQ ID NO:38.
14. An isolated antibody or antigen-binding fragment thereof that comprises the full length V H of 2G10 (SEQ ID NO:16) and a full length V L , wherein the full length V L comprises:
a V L CDR1 comprising the amino acid sequence of SEQ ID NO:34;
a V L CDR2 comprising the amino acid sequence of SEQ ID NO:36; and
a V L CDR3 comprising the amino acid sequence of SEQ ID NO:38.
15. An isolated antibody or antigen-binding fragment thereof that comprises a full length V H and the full length V L of 2G10 (SEQ ID NO:17), wherein the full length V H comprises:
a V H CDR1 comprising the amino acid sequence of SEQ ID NO:40
a V H CDR2 comprising the amino acid sequence of SEQ ID NO:42 and
a V H CDR3 comprising the amino acid sequence of SEQ ID NO:44.