The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize α v β 6 integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-α v β 6 antibodies of the invention. The invention also relates to the identification of differential expression of the integrin α v β 6 on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin α v β 6 .
1. A humanized antibody that specifically binds to α v β 6 comprising a heavy chain variable domain sequence of SEQ ID NO: 1 and a light chain variable domain of SEQ ID NO: 2.
2. A humanized antibody that specifically binds α v β 6 wherein said humanized antibody comprises a heavy chain variable domain selected from the group consisting of SEQ ID NO:144, SEQ ID NO:145, or SEQ ID NO:146 and a light chain variable domain sequence selected from the group consisting of SEQ ID NO: 139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID N:142 and SEQ ID NO:143.
3. A humanized antibody that specifically binds α v β 6 wherein said humanized antibody comprises a heavy chain variable domain sequence of SEQ ID NO:146 and a light chain variable domain sequence of SEQ ID NO:141 or SEQ ID NO:143.
4. A humanized antibody that specifically binds α v β 6 , wherein said antibody comprises a heavy chain variable domain (HV2) sequence of SEQ ID NO:145 and a light chain variable domain of SEQ ID NO:140.
5. A humanized antibody that specifically binds to α v β 6 and comprises a heavy chain variable domain sequence of SEQ ID NO: 146 (HV3) and a light chain variable domain of SEQ ID NO: 143 (LV5).
6. A humanized antibody that specifically binds to α v β 6 comprising a heavy chain variable domain sequence of SEQ ID NO: 3 and a light chain variable domain of SEQ ID NO: 4.
7. The humanized antibody of claim 2 , wherein said antibody comprises a heavy chain variable domain (HV1) sequence of SEQ ID NO:144 and a light chain variable domain sequence of SEQ ID NO:139.
8. A humanized antibody that specifically binds to α v β 6 comprising a variant of a heavy chain variable domain sequence of SEQ ID NO: 1 and/or a variant of a light chain variable domain of SEQ ID NO: 2, wherein said variant of SEQ ID NO: 1 comprises one or both of Q3M and N73S and said variant of SEQ ID NO:2 comprises one or more of the variations selected from the group consisting of L48W, I59V, A61V and Y88F as compared to SEQ ID NO:2.
9. A humanized antibody that specifically binds α v β 6 wherein said humanized antibody comprises a heavy chain variable domain sequence selected from the group consisting of SEQ ID NO:78, SEQ ID NO:79, and SEQ ID NO:80 and the light chain variable domain sequence selected from the group consisting of SEQ ID NO:75, SEQ ID NO:76, and SEQ ID NO:77.
10. A humanized antibody that specifically binds α v β 6 wherein said humanized antibody comprises a light chain variable domain sequence of SEQ ID NO:75 and a heavy chain variable domain sequence of SEQ ID NO:78.
11. A humanized antibody that specifically binds α v β 6 wherein said humanized antibody comprises a light chain variable domain sequence of SEQ ID NO:76 and a heavy chain variable domain sequence of SEQ ID NO:79.
12. A humanized antibody that specifically binds α v β 6 wherein said humanized antibody comprises a light chain variable domain sequence of SEQ ID NO:77 and a heavy chain variable domain sequence of SEQ ID NO:80.
13. A composition comprising the antibody of any one of claims 1 , 2 , 3 , 7 , 4 , 5 , 8 , 9 , 10 , 11 , and 12 , and a pharmaceutically acceptable carrier.
14. A composition comprising the antibody of claim 6 and a pharmaceutically acceptable carrier.