Integrin α-Vβ8 neutralizing antibody
The present invention relates to αvβ8 antagonists, anti-αvβ8 antibodies or immunoconjugates for reducing TGFβ activation in an individual. Further provided are compositions comprising one of the αvβ8 antagonists, anti-αvβ8 antibodies or immunoconjugates, methods for using the compositions, and related subject matter.
1. An isolated antibody that specifically binds αvβ8, wherein the antibody has a heavy chain variable region which comprises a CDR1 sequence of SEQ ID NO: 5, a CDR2 sequence of SEQ ID NO: 6, and a CDR3 sequence of SEQ ID NO: 7, and a light chain variable region which comprises a CDR1 sequence of SEQ ID NO: 8, a CDR2 sequence of SEQ ID NO: 9, wherein Xaa in SEQ ID NO:9 is tyrosine, and a CDR3 sequence of SEQ ID NO: 10.
2. The isolated antibody of claim 1 , wherein the isotype of the antibody is IgG1, IgG2, IgG3 or IgG4.
3. The isolated antibody of claim 1 , wherein the antibody is a monoclonal antibody.
4. The isolated antibody of claim 1 , wherein the antibody is a human antibody.
5. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable excipient.
6. The isolated antibody of claim 1 , wherein the antibody has a light chain variable region of SEQ ID NO:4 and a heavy chain variable region of SEQ ID NO: 2.
7. The isolated antibody of claim 1 , wherein the antibody has a kappa light chain variable region and a gamma heavy chain variable region.
8. The isolated antibody of claim 1 , wherein the antibody has a lambda light chain variable region and a gamma heavy chain variable region.
9. The isolated antibody of claim 1 , wherein the antibody binds the β8 human integrin but does not bind to β8 mouse integrin.
10. The isolated antibody of claim 1 , wherein the antibody is a humanized antibody.
11. The isolated antibody of claim 1 , wherein the antibody is a chimeric antibody.
12. An isolated nucleic acid encoding the antibody of claim 1 .
13. An isolated expression vector comprising the nucleic acid of claim 12 .
14. An isolated host cell comprising the vector of claim 13 .