Compositions and methods for modulating responses mediated or associated with BTLA activity
View Patent ↗Herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and acts as a molecular switch that modulates T cell activation by propagating positive signals from the TNF related ligand, LIGHT (p30, TNFSF14), or inhibitory signals through the immunoglobulin superfamily member, B and T lymphocyte attenuator (BTLA). A novel binding site for BTLA is disclosed, located in cysteine-rich domain-1 of HVEM. BTLA binding site on HVEM overlaps with the binding site for the Herpes Simplex virus-1 envelope glycoprotein D (gD), but is distinct from where LIGHT binds, yet gD inhibits the binding of both ligands. A BTLA activating protein present in human cytomegalovirus is identified as UL144. UL144 binds BTLA, but not LIGHT, and inhibits T cell proliferation.
1. A method of selectively modulating a response mediated or associated with immunoregulatory molecule B-T lymphocyte attenuator (BTLA) activity or expression for treatment of a subject having or at risk of having inflammatory bowel disease (IBD), comprising administering an anti-BTLA agonist antibody that modulates a response mediated or associated with immunoregulatory molecule B-T lymphocyte attenuator (BTLA) activity or expression to the subject.
2. The method of claim 1 , wherein the antibody comprises an agonist of BTLA activity.
3. The method of claim 1 , wherein the antibody increases a response mediated or associated with immunoregulatory molecule B-T lymphocyte attenuator (BTLA) activity or expression.
4. The method of claim 3 , wherein the response comprises inhibiting or reducing inflammation.
5. The method of claim 3 , wherein the response comprises inhibiting or reducing proliferation, survival, differentiation, death, or activity of T cells, antigen presenting cells or B cells.
6. The method of claim 3 , wherein the response comprises inhibiting or reducing cytotoxic or helper activity of activated T cells; or B cell production of antibody.
7. The method of claim 1 , wherein the subject is a human.
8. The method of claim 1 , wherein the inflammatory bowel disease comprises ulcerative colitis, or Crohn's disease.
9. The method of claim 1 , wherein the inflammatory bowel disease is associated with or caused by undesirable or aberrant proliferation, survival, differentiation, death, or activity of a T cell, antigen presenting cell or B cell.
10. The method of claim 1 , wherein the method reduces the occurrence, frequency, severity, progression, or duration of a symptom caused by or associated with IBD.
11. The method of claim 1 , wherein the method reduces gut or bowel infiltration or tissue destruction.
12. The method of claim 1 , wherein the anti-BTLA agonist antibody is monoclonal.
13. The method of claim 1 , wherein the anti-BTLA agonist antibody is mammalian.
14. The method of claim 1 , wherein the anti-BTLA agonist antibody is human.
15. The method of claim 1 , wherein the anti-BTLA agonist antibody is humanized.
16. The method of claim 1 , wherein the anti-BTLA agonist antibody comprises an IgG, IgA, IgM, IgE or IgD.
17. The method of claim 1 , wherein the anti-BTLA agonist antibody comprises a subsequence or a fragment that binds to BTLA.