Anti-PSGL-1 antibodies and methods of inducing cell death of an activated T cell
Immunoglobulin chains or antibodies having light or heavy chain complementarity determining regions of antibodies that bind to P-Selectin Glycoprotein Ligand-1. Also disclosed are methods of inducing death of an activated T-cell and of modulating a T cell-mediated immune response in a subject.
1. An antibody, comprising a first immunoglobulin chain and a second immunoglobulin chain, wherein the first chain, which is a light chain, and the second chain, which is a heavy chain, contain, respectively, SEQ ID NOs: 7-9 and SEQ ID NOs: 10-12; or SEQ ID NOs: 13-15 and SEQ ID NOs: 16-18, wherein the antibody binds specifically to human P-Selectin Glycoprotein Ligand 1.
2. An antibody that binds specifically to human P-Selectin Glycoprotein Ligand 1, wherein the antibody comprises
(i) a light chain variable region of SEQ ID NO: 21 and a heavy chain variable region of SEQ ID NO: 22, or
(ii) a light chain variable region of SEQ ID NO: 23 and a heavy chain variable region of SEQ ID NO: 24.
3. An antibody of claim 1 , wherein the antibody binds specifically to amino acid residues 50-60 of mature human P-Selectin Glycoprotein Ligand 1.
4. The antibody of claim 1 , wherein the antibody, upon binding to P-Selectin Glycoprotein Ligand 1 on an activated T-cell, induces the death of the activated T-cell.
5. A method of inducing death of an activated T-cell, comprising contacting an antibody of claim 1 with an activated T cell, wherein binding of the antibody to the activated T cell induces death of the activated T cell.
6. A method of inhibiting a T cell-mediated immune response in a subject, the method comprising:
administering to a subject having or being at risk of having a condition related to an excessive T cell-mediated immune response an effective amount of an antibody of claim 1 , wherein the condition is an inflammatory disease, an autoimmune disease, an allergic disease, or a T cell cancer.
7. The method of claim 6 , wherein the subject has received or is contemplated to receive an allogeneic or xenogeneic transplant.
8. An isolated antibody that binds specifically to human P-Selectin Glycoprotein Ligand 1, wherein the antibody comprises (i) a light chain comprising a variable region of SEQ ID NO: 21 or SEQ ID NO: 23 linked to a human kappa light chain constant region, and (ii) a heavy chain comprising a variable region of SEQ ID NO: 22 or SEQ ID NO: 24.
9. The antibody of claim 8 , wherein the antibody comprises a heavy chain constant region of human IgG1, IgG2 or IgG4.
10. A composition comprising the antibody according to claim 1 .
11. An antibody of claim 2 , wherein the antibody binds specifically to amino acid residues 50-60 of mature human P-Selectin Glycoprotein Ligand 1.
12. The antibody of claim 2 , wherein the antibody, upon binding to P-Selectin Glycoprotein Ligand 1 on an activated T-cell, induces the death of the activated T-cell.
13. A method of inducing death of an activated T-cell, comprising contacting an antibody of claim 2 with an activated T cell, wherein binding of the antibody to the activated T cell induces death of the activated T cell.
14. A method of inhibiting a T cell-mediated immune response in a subject, the method comprising:
administering to a subject having or being at risk of having a condition related to an excessive T cell-mediated immune response an effective amount of an antibody of claim 2 , wherein the condition is an inflammatory disease, an autoimmune disease, an allergic disease, or a T cell cancer.
15. The method of claim 14 , wherein the subject has received or is contemplated to receive an allogeneic or xenogeneic transplant.
16. A composition comprising the antibody according to claim 2 .