ANTIBODIES TO INTEGRIN AVB6 AND USE OF SAME TO TREAT CANCER
The invention provides antibodies that specifically bind to integrin αvβ6. The antibodies are useful for treatment and diagnoses of various cancers as well as detecting αvβ6.
1 . A humanized antibody that specifically binds to the human integrin αvβ6 wherein the antibody comprises a mature heavy chain region having a heavy chain variable region having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 11 or 22, and a light chain variable region having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25.
2 . The antibody of claim 1 , comprising a mature heavy chain region having a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 11 or 22, and a mature light chain variable region having the amino acid sequence set forth in SEQ ID NO: 25.
3 . The antibody of claim 1 wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.
4 . The antibody of claim 3 , wherein the heavy chain constant region is a mutant form of a natural human constant region which has reduced binding to an Fc gamma receptor relative to the natural human constant region.
5 . The antibody of claim 3 , wherein the heavy chain constant region is of IgG1 isotype.
6 . The antibody of claim 1 , wherein the antibody is conjugated to a cytotoxic or cytostatic agent.
7 . The antibody of claim 6 , wherein the cytotoxic agent is vcMMAE or mcMMAF.
8 . A method of treating a patient having pancreatic cancer or head and neck cancer, comprising administering to the patient an effective regime of an antibody of claim 1 .
9 . A pharmaceutical composition comprising an antibody of claim 1 .
10 . An isolated polynucleotide comprising a sequence encoding a heavy chain variable region and a light chain variable region as defined in claim 1 .
11 . An isolated vector comprising the polynucleotide of claim 10 .
12 . An isolated host cell comprising the vector of claim 11 .
13 . A method of making an anti-αvβ6 antibody or antigen binding fragment thereof, wherein the method comprises:
a) culturing the host cell of claim 12 under conditions suitable for expression of the polynucleotide encoding the antibody or antigen binding fragment thereof; and
b) isolating the antibody or antigen binding fragment thereof.
14 . A method of making an anti-αvβ6 antibody drug conjugate, wherein the method comprises:
a) culturing the host cell of claim 12 under conditions suitable for expression of the polynucleotide encoding the antibody or antigen binding fragment thereof;
b) isolating the antibody or antigen binding fragment thereof; and
c) conjugating a cytotoxic agent to the antibody or antigen binding fragment thereof.