Anti-αVβ6 antibodies and antibody-drug conjugates
Provided are novel anti-αvβ6 antibodies and antibody-drug conjugates and methods of using such anti-αvβ6 antibodies and antibody-drug conjugates to treat cancer.
1. A nucleic acid encoding a mature heavy chain variable region and/or a mature light chain variable region of an anti-avb6 antibody, or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises the mature heavy chain and the mature light chain variable region, wherein the heavy chain variable region comprises complementary determining regions (CDRs) comprising the amino acid sequences of SEQ ID NOs: 31, 32, and 33, and the mature light chain variable region comprises CDRs comprising the amino acid sequences of SEQ ID NOs: 37, 42, and 39.
2. The nucleic acid of claim 1 , wherein the antibody or antigen-binding fragment thereof is humanized.
3. The nucleic acid of claim 2 , wherein the mature heavy chain variable region comprises positions H2, H28, H48, H67, H69, H71, H73, H78, and H93, wherein position H2 is occupied by F, position H28 is occupied by S, position H48 is occupied by I, position H67 is occupied by A, position H69 is occupied by L, position H71 is occupied by V, position H73 is occupied by K, position H78 is occupied by A, and position H93 is occupied by T, and wherein the mature light chain variable region comprises positions L69, and L71, wherein position L69 is occupied by R, and position L71 is occupied by Y, and wherein the numbering is via the Kabat numbering system.
4. The nucleic acid of claim 1 , wherein the heavy chain variable region comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 6 and the light chain variable region comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 17.
5. The nucleic acid of claim 1 , wherein the heavy chain variable region comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 6 and the light chain variable region comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 17.
6. The nucleic acid of claim 1 , wherein the heavy chain variable region comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 6 and the light chain variable region comprises an amino acid sequence having at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 17.
7. The nucleic acid of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 6 and the light chain variable region comprises the amino acid sequence of SEQ ID NO:17.
8. The nucleic acid of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain and a light chain, wherein the heavy chain has an amino acid sequence comprising SEQ ID NO:21 and the light chain has an amino acid sequence comprising SEQ ID NO:29.
9. A vector comprising the nucleic acid of claim 8 .
10. A host cell comprising the vector of claim 9 .
11. The nucleic acid of claim 1 , wherein the antibody or antigen-binding fragment is an antigen-binding fragment, and wherein the antigen-binding fragment is selected from the group consisting of Fab, Fab′, F(ab′) 2 , Fab′-SH, Fv, diabody, linear antibody, and single-chain antibody fragment.
12. The nucleic acid of claim 1 , wherein the heavy chain variable region of the antibody is fused to a heavy chain constant region and the light chain variable region is fused to a light chain constant region.
13. The nucleic acid of claim 12 , wherein the heavy chain constant region is of the IgG1 isotype.
14. A vector comprising the nucleic acid of claim 1 .
15. A host cell comprising the vector of claim 14 .