Mucosal vascular addressins and uses thereof
The present invention relates to isolated antibodies and antigen-binding fragments thereof that bind naturally occurring human MAdCAM, wherein said naturally occurring human MAdCAM comprises a polypeptide with at least 90% sequence identity to SEQ ID NO:2 or SEQ ID NO:4, said naturally occurring human MAdCAM binds α4β7, and wherein said isolated antibodies and antigen-binding fragments thereof inhibit binding of said naturally occurring human MAdCAM to human α4β7, and wherein said antibody inhibits adhesion of RPMI 8866 cells to cells that express said human MAdCAM.
1. An isolated antibody or antigen-binding fragment thereof that binds naturally occurring human MAdCAM, wherein said naturally occurring human MAdCAM comprises a polypeptide with at least 90% sequence identity to SEQ ID NO:2 or SEQ ID NO:4, said naturally occurring human MAdCAM binds α4β7, and wherein said isolated antibody or antigen-binding fragment thereof inhibits binding of said naturally occurring human MAdCAM to human α4β7, and wherein said antibody inhibits adhesion of RPMI 8866 cells to cells that express said human MAdCAM.
2. The isolated antibody or antigen-binding fragment of claim 1 , wherein said human MAdCAM comprises amino acids 19-406 of SEQ ID NO:2.
3. The isolated antibody or antigen-binding fragment of claim 1 , wherein said human MAdCAM comprises amino acids 19-382 of SEQ ID NO:4.
4. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody or antigen-binding fragment selectively binds to the extracellular region of human MAdCAM.
5. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody or antigen-binding fragment selectively binds amino acids 19-225 of SEQ ID NO:2.
6. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody or antigen-binding fragment selectively binds amino acids 19-225 of SEQ ID NO:4.
7. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody inhibits α4β7-dependent adhesion.
8. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 and a physiologically acceptable carrier.
9. An isolated cell that produces an antibody or antigen-binding fragment of claim 1 .
10. A method of treating an inflammatory disease of mucosal tissue, comprising administering an effective amount of the antibody or antigen-binding fragment of claim 1 .
11. The method of claim 10 , wherein said inflammatory disease is inflammatory bowel disease.
12. A method of detecting naturally occurring human MAdCAM in a sample, comprising contacting said sample with an antibody or antigen-binding fragment of claim 1 , and detecting antibody-MAdCAM or antigen-binding fragment-MAdCAM complexes which are formed.
13. The isolated antibody of claim 1 , wherein said human MAdCAM comprises SEQ ID NO:17.
14. The isolated antibody or antigen-binding fragment of claim 1 , wherein said antibody or antigen-binding fragment does not inhibit binding of RAMOS cells to cells expressing VCAM-1.