Antibody targeting BCMA, bispecific antibody, and use thereof
Provided are an antibody targeting BCMA, a bispecific antibody targeting BCMA and CD3, and applications thereof. The antibody targeting BCMA comprises two heavy chain variable regions, the heavy chain variable regions comprising HCDR1, HCDR2, and HCDR3 as shown in the amino acid sequences of SEQ ID NO: 22, SEQ ID NO: 33 and SEQ ID NO: 42, or HCDR1, HCDR2, and HCDR3 as shown in the amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 37 and SEQ ID NO: 41. The antibody effectively targets human BCMA and binds to cynomolgus BCMA; the bispecific antibody effectively targets both human BCMA and human CD3, and can bind to cynomolgus BCMA and cynomolgus CD3.
1 . A monoclonal antibody or antigen-binding fragments thereof targeting BCMA comprising a heavy chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 37 and SEQ ID NO: 41, respectively.
2 . The monoclonal antibody or antigen-binding fragments thereof targeting BCMA of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 60.
3 . An isolated nucleic acid encoding the monoclonal antibody or antigen-binding fragments thereof targeting BCMA of claim 1 .
4 . An isolated expression vector comprising the isolated nucleic acid of claim 3 .
5 . An isolated host cell comprising the isolated expression vector of claim 4 .
6 . An antibody drug conjugate comprising the monoclonal antibody or antigen-binding fragments thereof targeting BCMA of claim 1 , and a cytotoxic agent.
7 . A pharmaceutical composition comprising the monoclonal antibody or antigen-binding fragments thereof targeting BCMA of claim 1 , and a pharmaceutically acceptable carrier.
8 . A method for treating cancer in a subject in need thereof, comprising: administering an effective amount of the monoclonal antibody or antigen-binding fragments thereof targeting BCMA of claim 1 to the subject.
9 . A method for treating cancer in a subject in need thereof, comprising: administering an effective amount of the antibody drug conjugate of claim 6 to the subject.
10 . The monoclonal antibody or antigen-binding fragment thereof targeting BCMA of claim 2 , wherein the antibody targeting BCMA further comprises an Fc fragment.
11 . The monoclonal antibody targeting BCMA of claim 10 , wherein the Fc fragment is an Fc fragment of hIgG1, hIgG2, hIgG3 or hIgG4 or a mutant thereof, the mutant of the human heavy chain constant region being selected from the group consisting of: (1) L234A/L235A mutation; (2) knob mutation T366W and hole mutations T366S, L368A and Y407V; (3) knob mutation S354C and hole mutation Y349C.
12 . The monoclonal antibody or antigen-binding fragment thereof targeting BCMA of claim 2 , the heavy chain of the antibody targeting BCMA has an amino acid sequence of SEQ ID NO: 7.
13 . The isolated host cell of claim 5 , wherein the isolated host cell is a prokaryotic cell or a eukaryotic cell.