Anti-glypican-3 antibody
An anti-glypican-3 antibody comprising one or more amino acid substitutions introduced in the Fc region is disclosed. Preferably, in the anti-glypican-3 antibody, one or more of the amino acid residues at the positions 239, 298, 326, 330 and 332 in the Fc region are substituted with other amino acid residues. Since the Fc-modified anti-glypican-3 antibody of the invention exhibit enhanced ADCC activity, it is useful in treating cancers, such as hepatic cancer. Also disclosed are an anticancer agent comprising the anti-glypican-3 antibody of the invention and a pharmaceutically acceptable carrier, as well as a method of treating a patient with cancer comprising administering to the patient the anticancer agent of the invention.
1. An anti-glypican-3 antibody that comprises a H-chain CDR1 as set forth in SEQ ID NO: 23, a H-chain CDR2 as set forth in SEQ ID NO: 24, and a H-chain CDR3 as set forth in SEQ ID NO: 25; and an L-chain CDR1 as set forth in SEQ ID NO: 26, an L-chain CDR2 as set forth in SEQ ID NO: 27, and an L-chain CDR3 as set forth in SEQ ID NO: 28; and further comprises either (a) or (b):
(a) an Fc region with aspartic acid at position 239, threonine at position 326, and glutamic acid at position 332 (all positions by EU numbering); or
(b) an Fc region with aspartic acid at position 239, alanine at position 298, glutamic acid at position 326, and glutamic acid at position 332 (all positions by EU numbering).
2. An anti-glypican-3 antibody that comprises a H-chain CDR1 as set forth in SEQ ID NO: 23, a H-chain CDR2 as set forth in SEQ ID NO: 24, and a H-chain CDR3 as set forth in SEQ ID NO: 25; and an L-chain CDR1 as set forth in SEQ ID NO: 26, an L-chain CDR2 as set forth in SEQ ID NO: 27, and an L-chain CDR3 as set forth in SEQ ID NO: 28; and further comprises either (a) or (b):
(a) an Fc region in which the amino acid residues at positions 239, 326 and 332 (all positions by EU numbering) are substituted with aspartic acid, threonine, and glutamic acid, respectively; or
(b) an Fc region in which the amino acid residues at positions 239, 298, 326 and 332 (all positions by EU numbering) are substituted with aspartic acid, alanine, glutamic acid, and glutamic acid, respectively.
3. An anticancer agent comprising the anti-glypican-3 antibody as claimed in claim 1 or 2 and a pharmaceutically acceptable carrier.
4. An anti-glypican-3 antibody that comprises a H-chain CDR1 as set forth in SEQ ID NO: 23, a H-chain CDR2 as set forth in SEQ ID NO: 24, and a H-chain CDR3 as set forth in SEQ ID NO: 25; and an L-chain CDR1 as set forth in SEQ ID NO: 26, an L-chain CDR2 as set forth in SEQ ID NO: 27, and an L-chain CDR3 as set forth in SEQ ID NO: 28; and further comprises (a) or (b):
(a) a CH2-CH3 domain comprising the amino acid sequence set forth in SEQ ID NO: 37; or
(b) a CH2-CH3 domain comprising the amino acid sequence set forth in SEQ ID NO: 38.
5. The anti-glypican-3 antibody of claim 1 , wherein the antibody comprises (a).
6. An anticancer agent comprising the antibody of claim 5 and a pharmaceutically acceptable carrier.
7. The anti-glypican-3 antibody of claim 1 , wherein the antibody comprises (b).
8. An anticancer agent comprising the antibody of claim 7 and a pharmaceutically acceptable carrier.
9. The anti-glypican-3 antibody of claim 4 , wherein the antibody comprises (a).
10. The anti-glypican-3 antibody of claim 4 , wherein the antibody comprises (b).