Anti-HER2 antibody and conjugate thereof
Disclosed are an anti-HER2 antibody and conjugate of the anti-HER2 antibody and small molecule medicine. Also disclosed are uses of the antibody and conjugate thereof in preparing medicine for treating tumor.
1. An antibody or functional fragments thereof which can specifically bind to HER2, wherein the antibody comprises a heavy chain and a light chain, in which:
(i) the heavy chain comprises three CDR regions, wherein the CDR regions have the amino acid sequence as shown in SEQ ID NO: 1, 2 and 3, respectively; and
(ii) the light chain comprises three CDR regions, wherein the CDR regions have the amino acid sequence as shown in SEQ ID NO: 4, 5 and 6, respectively.
2. The antibody or functional fragments thereof according to claim 1 , wherein the antibody is an antibody secreted from the hybridoma cells which were deposited at the China General Microbiological Culture Collection Center on Aug. 22, 2013, with the deposit number of CGMCC No. 8102.
3. The antibody or functional fragments thereof according to claim 1 , wherein the antibody is a humanized antibody.
4. The antibody or functional fragments thereof according to claim 1 , wherein the antibody is secreted from the CHO cells which were deposited at the China Center for Type Culture Collection on Nov. 6, 2013, with the deposit number of CCTCC C2013170.
5. An isolated polynucleotide, which encodes the antibody or functional fragments thereof according to claim 1 .
6. A combination of the isolated polynucleotides, which comprises: a polynucleotide encoding the light chain of the antibody or functional fragments thereof according to claim 1 and a polynucleotide encoding the heavy chain of the antibody or functional fragments thereof according to claim 1 .
7. A conjugate, which comprises the antibody or functional fragments thereof according to claim 1 which are conjugated with one or more therapeutic agents.
8. The conjugate according to claim 7 , wherein the therapeutic agent is coupled with the antibody or the functional fragments thereof through a linker Previously presented.
9. The conjugate according to claim 7 , wherein the conjugate has the general formula of Ab-(L-U)n, in which Ab represents the antibody or functional fragments thereof according to claim 1 , L represents a linker, U represents a therapeutic agent, and n represents an integer from 1 to 8.
10. A pharmaceutical composition, which comprises the antibody or functional fragments thereof according to claim 1 and/or the conjugate according to claim 7 , as well as a pharmaceutically acceptable carrier.
11. The conjugate according to claim 7 , wherein the therapeutic agent is selected from cytotoxic drug, immunopotentiators and radioactive isotopes.
12. The conjugate according to claim 7 , wherein the therapeutic agent is selected from dolastatin and derivatives thereof.
13. The conjugate according to claim 7 , wherein the therapeutic agent is selected from MMAE and MMAF.
14. The conjugate according to claim 8 , wherein the linker is linked with the antibody through thiol.
15. The conjugate according to claim 8 , wherein the linker is selected from mc-vc-pAB or mc.
16. A method for treating cancer, comprising administering the pharmaceutical composition according to claim 10 in a therapeutically effective amount to a subject in need thereof.
17. The method according to claim 16 , wherein the cancer is HER2-positive cancer.
18. The method according to claim 17 , wherein the cancer is breast cancer, ovary cancer or gastric cancer.
19. The method according to claim 17 , wherein the cancer is Lapatinib- and/or trastuzumab-resistant breast cancer, ovary cancer or gastric cancer.