Antibody binding to carbonic anhydrase and use thereof
Provided is an antibody that recognizes and binds to carbonic anhydrase or antigen-binding fragment, a nucleic acid molecule coding for the antibody or antigen-binding fragment, a vector carrying the nucleic acid molecule, a host cell including the nucleic acid molecule or the vector, and use of the antibody or antigen-binding fragment thereof in the alleviation, prevention, treatment or diagnosis of solid cancers.
1. An antibody or antigen-binding fragment thereof binding to carbonic anhydrase 12 (CA XII), comprising a VH-CDR1 having the amino acid sequence of SEQ ID NO: 14, a VH-CDR2 having the amino acid sequence of SEQ ID NO: 15, a VH-CDR3 having the amino acid sequence of SEQ ID NO: 28, a VL-CDR1 having the amino acid sequence of SEQ ID NO: 32 or 33, a VL-CDR2 having the amino acid sequence selected from the group consisting of SEQ ID NO: 34 to 42, and a VL-CDR3 having the amino acid sequence of SEQ ID NO: 31.
2. The antibody or antigen-binding fragment according to claim 1 , wherein the antibody further comprises VH-framework sequence comprising the amino acid sequences of SEQ ID NOs: 43 to 46.
3. The antibody or antigen-binding fragment according to claim 1 , wherein the antibody further comprises VL-framework sequence comprising the amino acid sequences of SEQ ID NOs: 47, 48, 51 and 52.
4. The antibody or antigen-binding fragment according to claim 3 , wherein the antibody further comprises VL-framework sequences comprising the amino acid sequence of SEQ ID NO: 48 which comprises the amino acid sequence of SEQ ID NO: 49 or 50.
5. The antibody or antigen-binding fragment according to claim 1 , wherein the antibody comprises VH-region amino acid sequence comprising the amino acid sequence of SEQ ID NO: 53, and VL-region amino acid sequence comprising the amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOs: 54 to 63.
6. The antibody or antigen-binding fragment according to claim 1 , wherein the antibody has an agonist activity to CA XII.
7. The antibody or antigen-binding fragment according to claim 1 , wherein the antigen-binding fragment is scFv, (scFv)2, Fab, Fab′ or F(ab′)2 of the anti-CA-XII antibody.
8. The antibody or antigen-binding fragment according to claim 1 , wherein the antibody or the antigen-binding fragment is coupled to labeling agent, toxin, or anti-tumor agent.
9. The antibody or antigen-binding fragment according to claim 8 , wherein the labeling agent is selected from the group consisting of a radioisotope, a hapten, a fluorescent material, a chromogen, and a dye.
10. The antibody or antigen-binding fragment according to claim 8 , wherein the toxin is a radioisotope, a small molecule, a peptide or a protein.
11. The antibody or antigen-binding fragment according to claim 8 , wherein the antibody or antigen-binding fragment is coupled with a toxin to form a fusion protein.
12. The antibody or antigen-binding fragment according to claim 8 , wherein the fucoses bound to the antibody or antigen-binding fragment are partly or completely removed.
13. A nucleic acid molecule encoding the antibody or antigen-binding fragment according to claim 1 .
14. A vector introduced by a nucleic acid molecule encoding the antibody or antigen-binding fragment according to claim 1 .
15. A host expressing the antibody or antigen-binding fragment according to claim 1 .
16. A pharmaceutical composition for prevention, alleviation or treatment of solid cancer, comprising the antibody or antigen-binding fragment according to claim 1 .
17. The pharmaceutical composition according to claim 16 , further comprising an anti-cancer chemical drug or other anti-cancer antibody.
18. A composition for detecting a solid cancer, comprising the antibody or antigen-binding fragment according to claim 1 , wherein a sample is determined as the solid cancer if the sample shows a positive reaction to the antibody or antigen-binding fragment.
19. The composition for detecting a solid cancer according to claim 18 , wherein the antibody or the antigen-binding fragment is coupled to a labeling agent.