Anti-HER2/anti-4-1BB bispecific antibody and use thereof
Provided are an anti-4-1BB/anti-HER2 bispecific antibody, and a pharmaceutical composition and a method for treating and/or preventing a cancer using the same.
1. An anti-4-1 BB/anti-HER2 bispecific antibody comprising:
(a) an anti-4-1 BB antibody or an antigen-binding fragment thereof, wherein the anti-4-1 BB antibody or the antigen-binding fragment thereof is an anti-4-1 BB scFv of the anti-4-1 BB antibody, and
(b) an anti-HER2 antibody or an antigen-binding fragment thereof, wherein the anti-HER2 antibody or an antigen-binding fragment thereof is a full-length form of the anti-HER2 antibody, and the anti-4-1 BB scFv is linked at its N-terminus to the C-terminus of a heavy chain of the anti-HER2 antibody,
wherein the anti-4-1 BB antibody or the antigen-binding fragment thereof comprises:
(1) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 18 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30, or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 24 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 33;
(2) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 19 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 or 31, or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 25 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 33 or 34;
(3) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30 or 31; or
(4) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 21 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30,
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 22 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 31,
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 27 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 33, or
a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 34, and
wherein the anti-HER2 antibody or an antigen-binding fragment thereof comprises:
a heavy chain comprising the amino acid sequence of SEQ ID NO: 73; and
a light chain comprising the amino acid sequence of SEQ ID NO: 75.
2. The anti-4-1BB/anti-HER2 bispecific antibody of claim 1 , wherein the anti-4-1BB scFv further comprises a peptide linker between the heavy chain variable region and the light chain variable region.
3. The anti-4-1BB/anti-HER2 bispecific antibody of claim 1 , wherein the anti-HER2 antibody is Trastuzumab, or Trastuzumab emtansine (T-DM1).
4. A pharmaceutical composition comprising the anti-4-1BB/anti-HER2 bispecific antibody of claim 1 and a pharmaceutically acceptable carrier.
5. The anti-4-1BB/anti-HER2 bispecific antibody of claim 1 , wherein the anti-4-1BB/anti-HER2 bispecific antibody comprises:
a polypeptide comprising the amino acid sequence of SEQ ID NO: 83, or 84; and
a polypeptide comprising the amino acid sequence of SEQ ID NO: 75.
6. The anti-4-1BB/anti-HER2 bispecific antibody of claim 1 , wherein the anti-4-1BB/anti-HER2 bispecific antibody comprises:
a polypeptide comprising the amino acid sequence of SEQ ID NO: 83; and
a polypeptide comprising the amino acid sequence of SEQ ID NO: 75.