Antibodies specific to cadherin-17
View Patent ↗The present disclosure provides antibodies, including isolated monoclonal antibodies, which specifically bind to Cadherin-17 with high affinity. Nucleic acid molecules encoding Cadherin-17 antibodies, expression vectors, host cells and methods for expressing the Cadherin-17 antibodies are also provided. Bispecific molecules and pharmaceutical compositions comprising the Cadherin-17 antibodies are also provided. Methods for detecting Cadherin-17, as well as methods for treating various cancers, including colorectal cancer, are disclosed.
1. An isolated anti-Cadherin-17 antibody comprising:
a. a heavy chain variable region comprising
i. a CDR1 of SEQ ID NO:4
ii. a CDR2 of SEQ ID NO:8 and
iii. a CDR3 of SEQ ID NO:17; and
b. a light chain variable region comprising
i. a CDR1 of SEQ ID NO:24
ii. a CDR2 of SEQ ID NO:30 and
iii. a CDR3 of SEQ ID NO:34.
2. The antibody of claim 1 , wherein said antibody is a full-length antibody of an IgG1, IgG2, IgG3, or IgG4 isotype.
3. The antibody of claim 1 , wherein said antibody is selected from the group consisting of: a whole antibody, a monoclonal antibody, an antibody fragment, a humanized antibody, a single chain antibody, a defucosylated antibody, an antibody mimetic and a bispecific antibody.
4. An isolated nucleic acid molecule encoding the heavy or light chain of the antibody of claim 1 .
5. An expression vector comprising the nucleic acid molecule of claim 4 .
6. A host cell comprising the expression vector of claim 5 .
7. A method for preparing an anti-Cadherin-17 antibody, said method comprising the steps of:
obtaining a host cell that contains one or more nucleic acid molecules encoding the antibody of claim 1 ;
growing the host cell in a host cell culture; providing host cell culture conditions wherein the one or more nucleic acid molecules are expressed; and
recovering the antibody from the host cell or from the host cell culture.
8. An isolated anti-Cadherin-17 antibody comprising a heavy chain variable region comprising the mature portion of SEQ ID NO:38 and a light chain variable region comprising the mature portion of SEQ ID NO:49.
9. An isolated anti-Cadherin-17 antibody according to claim 1 comprising a heavy chain variable region comprising SEQ ID NO: 138, or an amino acid sequence at least 95% identical thereto, and a light chain variable region comprising SEQ ID NO: 139, or an amino acid sequence at least 95% identical thereto.
10. The isolated anti-Cadherin-17 antibody of claim 8 , wherein the antibody comprises a heavy chain variable region comprising SEQ ID NO: 138 and a light chain variable region comprising SEQ ID NO: 139.
11. An immunoconjugate comprising an antibody according to any one of claims 1 and 8 - 10 conjugated to a therapeutic agent.
12. The immunoconjugate of claim 11 wherein the therapeutic agent is a cytotoxin.
13. A composition comprising the isolated antibody of any one of claims 1 and 8 - 10 and a pharmaceutically acceptable carrier.
14. A method for treating cancer associated with target cancer cells expressing Cadherin-17, said method comprising the step of administering to a subject the immunoconjugate of claim 11 , in an amount effective to treat the cancer.
15. The method of claim 14 , wherein said cancer is a human cancer.
16. The method of claim 15 , wherein said human cancer is colorectal cancer.
17. The method of claim 15 , wherein said human cancer is gastric cancer or pancreatic cancer.