Antibody binding specifically to human and mouse L1CAM protein, and use therefor
The present invention relates to a novel antibody specifically binding to human and mouse L1CAM, and more particularly, to an antibody binding to both human and mouse L1CAM with high affinity, which is prepared by modifying a sequence of an L1 cell adhesion molecule (L1CAM)-specific antibody comprising a heavy-chain variable region of SEQ ID NO. 1 and a light-chain variable region of SEQ ID NO. 5, a polynucleotide encoding the antibody, an expression vector comprising the polynucleotide, a transformant introduced with the vector, a pharmaceutical composition for preventing or treating cancer comprising the antibody, a method for treating cancer using the antibody, a composition for diagnosing cancer comprising the antibody, a kit for diagnosing cancer comprising the composition, a method for providing information for cancer diagnosis using the antibody, and an antibody-drug conjugate prepared by conjugating a drug to the antibody.
1. An antibody binding to human L1 cell adhesion molecule (L1CAM) protein, comprising:
a heavy-chain variable region comprising (i) a heavy chain CDR1 of SEQ ID NO. 2; (ii) a heavy chain CDR2 of SEQ ID NO. 9 or a heavy chain CDR2 of SEQ ID NO. 9 except for a substitution of glutamic acid for aspartic acid as an amino acid at position 5; and (iii) a heavy chain CDR3 of SEQ ID NO. 10; and
a light-chain variable region comprising (iv) a light chain CDR1 of SEQ ID NO. 6 or a light chain CDR1 of SEQ ID NO. 6 except for a substitution of serine for isoleucine as an amino acid at position 8; (v) a light chain CDR2 of SEQ ID NO. 7; and (vi) a light chain CDR3 of SEQ ID NO. 11 or a light chain CDR3 of SEQ ID NO. 15.
2. The antibody of claim 1 , wherein the antibody comprises a heavy-chain variable region comprising a heavy chain CDR1 of SEQ ID NO. 2, a heavy chain CDR2 of SEQ ID NO. 9, and a heavy chain CDR3 of SEQ ID NO. 10; and
a light-chain variable region comprising a light chain CDR1 of SEQ ID NO. 6, a light chain CDR2 of SEQ ID NO. 7, and a light chain CDR3 of SEQ ID NO. 11.
3. The antibody of claim 2 , wherein the antibody comprises a heavy-chain variable region of SEQ ID NO. 12 and a light-chain variable region of SEQ ID NO. 13.
4. The antibody of claim 1 , wherein the antibody comprises a heavy-chain variable region comprising a heavy chain CDR1 of SEQ ID NO. 2, a heavy chain CDR2 of SEQ ID NO. 9, and a heavy chain CDR3 of SEQ ID NO. 10; and
a light-chain variable region comprising a light chain CDR1 of SEQ ID NO. 6, a light chain CDR2 of SEQ ID NO. 7, and a light chain CDR3 of SEQ ID NO. 15.
5. The antibody of claim 4 , wherein the antibody comprises a heavy-chain variable region of SEQ ID NO. 12 and a light-chain variable region of SEQ ID NO. 14.
6. The antibody of claim 1 , wherein the antibody comprises a heavy-chain variable region comprising a heavy chain CDR1 of SEQ ID NO. 2, a heavy chain CDR2 of SEQ ID NO. 16, and a heavy chain CDR3 of SEQ ID NO. 10; and a light-chain variable region comprising a light chain CDR1 of SEQ ID NO. 17, a light chain CDR2 of SEQ ID NO. 7, and a light chain CDR3 of SEQ ID NO. 15.
7. The antibody of claim 6 , wherein the antibody comprises a heavy-chain variable region of SEQ ID NO. 18 and a light-chain variable region of SEQ ID NO. 19.
8. The antibody of claim 6 , wherein the antibody comprises a heavy-chain variable region of SEQ ID NO. 18 and a light-chain variable region of SEQ ID NO. 34.
9. The antibody of claim 1 , wherein the antibody comprises a heavy-chain variable region of SEQ ID NO. 12 or 18, and a light-chain variable region of SEQ ID NO. 14, 19, or 34.
10. The antibody of claim 1 , wherein the heavy-chain variable region of the antibody comprises (i) a heavy chain framework region 1 (FR1) of SEQ ID NO. 22 or a heavy chain FR1 of SEQ ID NO. 22 except for a substitution of glycine for arginine as an amino acid at position 16; (ii) FR2 of SEQ ID NO. 23; (iii) a heavy chain FR3 of SEQ ID NO. 24 or a heavy chain FR3 of SEQ ID NO. 24 except for a substitution of alanine for lysine as an amino acid at position 10 and a substitution of alanine for proline as an amino acid at position 22; and (iv) FR4 of SEQ ID NO. 25, and
the light-chain variable region thereof comprises (v) FR1 of SEQ ID NO. 28; (vi) a light chain FR2 of SEQ ID NO. 29 or a light chain FR2 of SEQ ID NO. 29 except for a substitution of glutamine for arginine as an amino acid at position 3, a substitution of lysine for arginine as an amino acid at position 5, and a substitution of glutamine for lysine as an amino acid at position 8; (vii) a light chain FR3 of SEQ ID NO. 30 or SEQ ID NO. 33, or a light chain FR3 of SEQ ID NO. 30 except for a substitution of isoleucine for valine as an amino acid at position 19 and a substitution of alanine for glycine as an amino acid at position 28; and (viii) a light chain FR4 of SEQ ID NO. 31.
11. An antibody binding to human L1 cell adhesion molecule (L1CAM) protein, comprising:
a heavy-chain variable region comprising (i) a heavy chain CDR1 of SEQ ID NO. 2; (ii) a heavy chain CDR2 selected from the group consisting of a heavy chain CDR2 of SEQ ID NO. 3, a heavy chain CDR2 of SEQ ID NO. 3 except for a substitution of phenylalanine for valine as an amino acid at position 1, and a heavy chain CDR2 of SEQ ID NO. 3 except for a substitution of phenylalanine for valine as an amino acid at position 1 and a substitution of glutamic acid for aspartic acid at position 5; and (iii) a heavy chain CDR3 of SEQ ID NO. 4 or a heavy chain CDR3 of SEQ ID NO. 4 except for a substitution of alanine for histidine as an amino acid at position 3; and
a light-chain variable region comprising (iv) a light chain CDR1 of SEQ ID NO. 6 or a light chain CDR1 of SEQ ID NO. 6 except for a substitution of serine for isoleucine as an amino acid at position 8; (v) a light chain CDR2 of SEQ ID NO. 7; and (vi) a light chain CDR3 selected from the group consisting of a light chain CDR3 of SEQ ID NO. 8, a light chain CDR3 of SEQ ID NO. 8 except for a substitution of alanine for aspartic acid as an amino acid at position 5, and a light chain CDR3 of SEQ ID NO. 15.
12. A polynucleotide encoding the antibody of claim 1 .
13. An expression vector comprising the polynucleotide of claim 12 .
14. A transformant comprising the expression vector of claim 13 .
15. A composition comprising the antibody of claim 1 .
16. The composition of claim 15 , wherein the composition is used for diagnosing cancer.
17. A method for diagnosing an L1CAM-expressing cancer, the method comprising: contacting a biological sample separated from an individual suspected of having an L1CAM-expressing cancer with the antibody of claim 1 ; and detecting formation of an antigen-antibody complex.
18. A kit for diagnosing cancer, comprising the composition of claim 15 .
19. An antibody-drug conjugate, wherein the drug is conjugated to the antibody of claim 1 .
20. A method for treating an L1CAM-expressing cancer, the method comprising administering the antibody of claim 1 to a subject in need thereof.