Antibodies and methods of use thereof
The disclosure relates to protease-binding agent specific for a protease. The agent may be an antibody capable of specifically binding and inhibiting a protease, such as a P1-Arg-specific protease. The disclosure also provides methods of producing, and compositions comprising the subject agent. Methods and kits related to the protease-binding agent find use in protection against, detection, diagnosing, treating cancer and infections due to pathogens containing active proteases.
1. A protease-binding antibody, comprising:
a) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 16;
b) a VLCDR2 comprising the amino acid sequence of SEQ ID NO: 17;
c) a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 18;
d) a VHCDR1 comprising the amino acid sequence of SEQ ID NO: 19;
e) a VHCDR2 comprising the amino acid sequence of SEQ ID NO: 20; and
f) a VHCDR3 comprising the amino acid sequence of SEQ ID NO: 10.
2. The protease-binding antibody of claim 1 , wherein said antibody comprises:
a) a light chain of at least 90% amino acid sequence identity to SEQ ID NO: 1; and
b) a heavy chain of at least 85% amino acid sequence identity to SEQ ID NO: 3.
3. The protease-binding antibody of claim 1 , wherein said protease is P1-Arg-specific protease.
4. The protease-binding antibody of claim 3 , wherein said P1-Arg- specific protease is a type II transmembrane serine protease.
5. The protease-binding antibody of claim 4 , wherein said type II transmembrane serine protease is membrane-type serine protease I.
6. The protease-binding antibody of claim 1 , wherein said protease-binding antibody is detectably labeled.
7. The protease-binding antibody of claim 1 , wherein said antibody is radiolabeled.
8. A pharmaceutical composition comprising the protease-binding antibody of claim 1 and a pharmaceutical acceptable excipient.
9. The pharmaceutical composition of claim 8 , wherein said composition further comprises an anti-cancer agent.
10. A method of detecting a cancer cell comprising a cell surface serine protease in a subject comprising:
contacting the protease-binding antibody of claim 1 with a cell of said subject suspected of being cancerous;
detecting said protease-binding antibody bound to said cell.
11. The method of claim 10 , wherein said detecting comprises imaging tissues of said subject.
12. The method of claim 10 , wherein said protease-binding antibody is radiolabeled.
13. The method of claim 10 , wherein said detecting comprises single photon emission computed tomography.
14. A method of inhibiting a serine protease comprising:
contacting the protease-binding antibody of claim 1 to said protease.
15. A kit for detecting cancer cells in a subject comprising:
the protease binding antibody of claim 1 .
16. The kit of claim 15 , wherein said protease binding antibody is radiolabeled.