Production of hersintuzumab: a new humanized antibody against HER2 for cancer treatment
A monoclonal anti-HER2 antibody is mutated on complementarity determining regions (CDRs) and framework regions. The VH domain of the antibody includes a portion of the amino acid sequence as SEQ ID NO: 1. The VL domain of the antibody includes a portion of the amino acid sequence as SEQ ID NO: 5.
1. A humanized monoclonal anti-HER2 antibody for treating cancer, comprising:
CDR-H1 comprising amino acid residues of 31-35 of SEQ ID NO: 1;
CDR-H2 comprising amino acid residues of 50-65 of SEQ ID NO: 1;
CDR-H3 comprising amino acid residues of 98-105 of SEQ ID NO: 1;
CDR-L1 comprising amino acid residues of 24-34 of SEQ ID NO: 5;
CDR-L2 comprising amino acid residues of 50-56 of SEQ ID NO: 5; and
CDR-L3 comprising amino acid residues of 89-97 of SEQ ID NO: 5.
2. The humanized monoclonal anti-HER2 antibody of claim 1 , further comprising:
(a) a heavy chain variable domain having at least 90% identity to the amino acid sequence of SEQ ID NO: 1;
(b) a light chain variable domain having at least 90% identity to the amino acid sequence of SEQ ID NO: 5; or
(c) a heavy chain variable domain according to (a) and a light chain variable domain according to (b).
3. The humanized monoclonal anti-HER2 antibody of claim 1 , wherein the heavy chain variable domain is identical to SEQ ID NO: 1.
4. The humanized monoclonal anti-HER2 antibody of claim 1 , wherein the light chain variable domain is identical to SEQ ID NO: 5.
5. The humanized monoclonal anti-HER2 antibody of claim 1 , wherein the humanized monoclonal anti-HER2 antibody is a Fab fragment, a F(ab)′2 fragment, or a single chain variable fragment (scFv).
6. The humanized monoclonal anti-HER2 antibody of claim 1 , wherein the humanized monoclonal anti-HER2 antibody is to treat breast cancer.
7. An antibody-drug conjugate for treating cancer comprising:
a humanized monoclonal anti-HER2 antibody conjugated to a drug, wherein the humanized monoclonal anti-HER2 antibody comprises:
CDR-H1 comprising amino acid residues of 31-35 of SEQ ID No: 1;
CDR-H2 comprising amino acid residues of 50-65 of SEQ ID No: 1;
CDR-H3 comprising amino acid residues of 98-105 of SEQ ID No: 1;
CDR-L1 comprising amino acid residues of 24-34 of SEQ ID No: 5;
CDR-L2 comprising amino acid residues of 50-56 of SEQ ID No: 5; and
CDR-L3 comprising amino acid residues of 89-97 of SEQ ID No: 5.
8. The antibody-drug conjugate of claim 7 , wherein the drug includes a cytotoxic agent.
9. The antibody-drug conjugate of claim 8 , wherein the humanized monoclonal anti-HER2 antibody specifically delivers the cytotoxic agent to cancer cells.
10. The antibody-drug conjugate of claim 8 , wherein the humanized monoclonal anti-HER2 antibody is configured to specifically bind to a tumor antigen expressed on a cancer cell surface.
11. The antibody-drug conjugate of claim 7 , wherein the drug includes an anti-microtubule agent.
12. The antibody-drug conjugate of claim 7 , wherein the drug includes an interstrand cross-linking agent.
13. The antibody-drug conjugate of claim 7 , wherein the antibody-drug conjugate is to treat breast cancer.
14. The humanized monoclonal anti-HER2 antibody of claim 1 , wherein the humanized monoclonal anti-HER2 antibody in hetero-conjugation with trastuzumab is to treat breast cancer.