Antibody binding specifically to MUC1 and use thereof
The present invention relates to an anti-MUC1 antibody binding specifically to Mucin 1 (MUC1) or an antigen-binding fragment thereof, an antibody-drug conjugate comprising the antibody or the antigen-binding fragment thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the conjugate. According to the present invention, the antibody shows outstanding affinity and binding force to MUC1 and the antibody-drug conjugate in which the antibody or the antigen-binding fragment thereof is conjugated with a drug can bind specifically to a MUC1-expressing cell to specifically or selectively transfer the drug with efficacy. Therefore, the anti-MUC1 antibody and the antibody-drug conjugate according to the present invention can be usefully applied to the treatment of a MUC1-related disease, for example, cancer.
1. An antibody-drug conjugate in which a drug is conjugated with an anti-MUC1 antibody or an antigen-binding fragment thereof,
wherein the anti-MUC1 antibody or the antigen-binding fragment thereof recognizes a polypeptide comprising at least five consecutive amino acids in a C-terminal extracellular domain of MUC1,
wherein the anti-MUC1 antibody or the antigen-binding fragment thereof comprises:
a heavy-chain CDR1 of SEQ ID NO: 1; heavy-chain CDR2 of SEQ ID NO: 2; and heavy-chain CDR3 of SEQ ID NO: 3; and
a light-chain CDR1 of SEQ ID NO: 4; light-chain CDR2 of SEQ ID NO: 5; and light-chain CDR3 of SEQ ID NO: 6.
2. The antibody-drug conjugate according to claim 1 , wherein the antibody or the antigen-binding fragment thereof recognizes an extracellular domain of MUC1 comprising the amino acid sequence SEQ ID NO: 8.
3. The antibody-drug conjugate according to claim 1 , wherein the antibody or the antigen-binding fragment thereof comprises:
a heavy-chain variable region of SEQ ID NO: 22 or 24; and
a light-chain variable region of SEQ ID NO: 23 or 25.
4. The antibody-drug conjugate according to claim 3 , wherein the antibody or the antigen-binding fragment thereof comprises:
a heavy-chain variable region of SEQ ID NO: 22 and a light-chain variable region of SEQ ID NO: 23; or
a heavy-chain variable region of SEQ ID NO: 24 and a light-chain variable region of SEQ ID NO: 25.
5. The antibody-drug conjugate according to claim 1 , wherein the anti-MUC1 antibody or the antigen-binding fragment thereof is linked to the drug via a linker.
6. The antibody-drug conjugate according to claim 5 , wherein the linker is a cleavable linker or a non-cleavable linker.
7. The antibody-drug conjugate according to claim 1 , wherein the drug is a chemotherapeutic agent, toxin, microRNA (miRNA), siRNA, shRNA or a radioactive isotope.
8. A pharmaceutical composition for treating cancer comprising the antibody-drug conjugate according to claim 1 .
9. The pharmaceutical composition for treating cancer according to claim 8 , wherein the cancer expresses a MUC1 protein.
10. The pharmaceutical composition for treating cancer according to claim 9 , wherein the cancer is breast cancer, pancreatic cancer, prostate cancer, lung cancer, thyroid cancer, stomach cancer, ovarian cancer, colorectal cancer, liver cancer, gallbladder cancer, kidney cancer, cervical cancer, or bladder cancer.