Bispecific antibody and uses thereof
Provided is a novel antibody and a method for treating breast cancer. More specifically, the present disclosure relates to a bispecific antibody targeting CD3 and a tumor antigen target such as HER2, a preparation method, and uses thereof. The present disclosure also relates to a composition containing said antibody and a method for treating cancer by using the antibody.
1. An antibody or antibody fragment, comprising an antigen binding domain that binds to CD3, wherein the antigen binding domain comprises a heavy chain variable domain (VH) having an amino acid sequence of SEQ ID NO: 21 and a light chain variable domain (VL) having an amino acid sequence of SEQ ID NO: 22.
2. The antibody or antibody fragment according to claim 1 , comprising a heavy chain sequence of SEQ ID NO: 9 and a light chain sequence of SEQ ID NO: 11.
3. The antibody or antibody fragment according to claim 1 , wherein the antibody is a bispecific antibody or a multi-specific antibody.
4. The antibody or antibody fragment according to claim 1 , further comprising an antigen binding domain for binding to an antigen target of a tumor.
5. The antibody or antibody fragment according to claim 4 , wherein the antigen target of a tumor is HER2.
6. The antibody or antibody fragment according to claim 5 , wherein the antibody comprises a heavy chain sequence selected from the group consisting of Her2-OB1 (SEQ ID NO: 1), Her2-OB2 (SEQ ID NO: 3), Her2-OB3 (SEQ ID NO: 5), and Her2-OB4 (SEQ ID NO: 7).
7. The antibody or antibody fragment according to claim 6 , wherein the antibody comprises a heavy chain sequence of Her2-OB4 (SEQ ID NO: 7).
8. The antibody or antibody fragment according to claim 1 , wherein the antibody fragment is selected from the group consisting of a Fab fragment, a Fab′ fragment, a Fd fragment, a Fd′ fragment, a Fv fragment, a dAb fragment, a F(ab′)2 fragment, and a scFv fragment.
9. A bispecific antibody, comprising a first heavy chain, a second heavy chain, and a light chain, wherein the first heavy chain has a scFv-hinge region-Fc from an N-terminus to a C-terminus; the second heavy chain has a VH-CH1-hinge region-Fc from an N-terminus to a C-terminus; and the light chain has a VL-CL from an N-terminus to a C-terminus; wherein an antigen binding domain of the scFv of the first heavy chain binds to an antigen target of a tumor, and the VH-CH1 of the second heavy chain and the VL-CL of the light chain form an antigen binding domain, which binds to a signal channel receptor on a surface of an immune effector cell; wherein the VH of the second heavy chain has a sequence of SEQ ID NO: 21, and the VL of the light chain has a sequence of SEQ ID NO: 22.
10. The bispecific antibody according to claim 9 , wherein the second heavy chain comprises a sequence of SEQ ID NO: 9, and the light chain comprises a sequence of SEQ ID NO: 11.
11. The bispecific antibody according to claim 9 , wherein the scFv of the first heavy chain comprises, from N-terminus to C-terminus, a VH region of a Ch4D5-monoclonal antibody, a connecting peptide and a VL region of the Ch4D5-monoclonal antibody; or comprises, from N-terminus to C-terminus, the VL region of a Ch4D5-monoclonal antibody, the connecting peptide and the VH region of the Ch4D5-monoclonal antibody.
12. The bispecific antibody according to claim 9 , wherein the first heavy chain comprises a sequence selected from the group consisting of Her2-OB1 (SEQ ID NO: 1), Her2-OB2 (SEQ ID NO: 3), Her2-OB3 (SEQ ID NO: 5) and Her2-OB4 (SEQ ID NO: 7).
13. The bispecific antibody according to claim 9 , wherein the first heavy chain comprises the sequence of Her2-OB4 (SEQ ID NO: 7).
14. The bispecific antibody according to claim 9 , wherein the CH2 of the first heavy chain is the CH2 of a heavy chain of a Ch4D5-monoclonal antibody containing L234A and L235A mutations.
15. The bispecific antibody according to claim 9 , wherein the first heavy chain, the second heavy chain, and/or the light chain are derived from IgG1, IgG2, IgG3 or IgG4.
16. The bispecific antibody according to claim 11 , wherein the connecting peptide is (GGGGS)×N, N=3, 4 or 5 (SEQ ID NO:s 23, 31, and 32 respectively).