Anti-HER2 antibody or antigen-binding fragment thereof, and chimeric antigen receptor comprising same
The present disclosure relates to a novel anti-HER2 antibody or an antigen-binding fragment thereof used in the prevention or treatment of cancer, a chimeric antigen receptor including the same, and uses thereof. The antibody of the present disclosure is an antibody that specifically binds to HER2 which is highly expressed in cancer cells (particularly, breast cancer or gastric cancer cells), and binds to an epitope that is different from an epitope to which trastuzumab binds.
1. A method for treating a HER2 positive cancer, the method comprising:
administering to a subject in need thereof
a therapeutically effective amount of a pharmaceutical composition comprising natural killer cells expressing a chimeric antigen receptor targeting human HER2, the chimeric antigen receptor comprising an amino acid sequence comprising, from N- to C-terminus:
an extracellular antigen binding domain comprising a heavy chain variable region comprising the amino acid sequences of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, and a light chain variable region comprising the amino acid sequences of SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12;
a CD8a hinge domain;
a CD28 transmembrane domain; and
an intracellular signaling domain comprising:
(i) a CD28 intracellular signaling domain,
(ii) a OX4OL intracellular signaling domain, and
(iii) a CD3z intracellular signaling domain; and
a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the OX4OL intracellular signaling domain comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 127.
3. The method of claim 2 , wherein the OX4OL intracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 127.
4. The method of claim 1 , wherein the CD3z intracellular signaling domain comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 121.
5. The method of claim 1 , wherein the CD3z intracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 121.
6. The method of claim 4 , wherein the CD28 intracellular signaling domain comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 125.
7. The method of claim 4 , wherein the CD28 intracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 125.
8. The method of claim 6 , wherein the CD28 transmembrane domain comprises an amino acid sequence having at least 90% sequence identity with SEQ ID NO: 119.
9. The method of claim 8 , wherein the CD28 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 119.
10. The method of claim 8 , wherein the CD8a hinge domain comprises an amino acid sequence having at least 90% identity with SEQ ID NO: 115.
11. The method of claim 10 , wherein the CD8a hinge domain comprises the amino acid sequence of SEQ ID NO: 115.
12. The method of claim 10 , wherein the chimeric antigen receptor further comprises a CD8a extracellular signaling domain.
13. The method of claim 12 , wherein the CD8a extracellular signaling domain comprises the amino acid sequence of SEQ ID NO: 111.
14. The method of claim 1 , wherein the extracellular antigen binding domain comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 113.
15. The method of claim 14 , wherein the extracellular antigen binding domain comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 113.
16. The method of claim 15 , wherein the extracellular antigen binding domain comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 113.
17. The method of claim 16 , wherein the extracellular antigen binding domain comprises the amino acid sequence of SEQ ID NO: 113.
18. The method of claim 13 , wherein the chimeric antigen receptor comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 135.
19. The method of claim 14 , wherein the chimeric antigen receptor comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 135.
20. The method of claim 15 , wherein the chimeric antigen receptor comprises an amino acid sequence having at least 99% sequence identity to SEQ ID NO: 135.
21. The method of claim 16 , wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 135.
22. The method of claim 1 , wherein the HER2 positive cancer is selected from the group consisting of breast cancer, ovarian cancer, gastric cancer, lung cancer, liver cancer, bronchial cancer, nasopharyngeal cancer, laryngeal cancer, pancreatic cancer, bladder cancer, colorectal cancer, colon cancer, cervical cancer, brain cancer, prostate cancer, bone cancer, head and neck cancer, skin cancer, thyroid cancer, parathyroid cancer and ureteral cancer.
23. The method of claim 18 , wherein the HER2 positive cancer is selected from the group consisting of breast cancer, ovarian cancer, and gastric cancer.
24. The method of claim 19 , wherein the HER2 positive cancer is trastuzumab resistant.