CD133-binding agents and uses thereof
This disclosure is directed to novel CD133-binding agents. The disclosure is also directed to uses of novel CD133-binding agents for detecting CD133-expressing cells and/or quantitating levels of cellular CD133 expression, for targeting CD133-expressing cells, for decreasing levels of CD133 in CD133-expressing cells and for treating or preventing cancer.
1. An antibody or an antigen binding fragment thereof that specifically binds to a CD133 polypeptide, wherein said antibody or antigen binding fragment thereof comprises a light chain variable domain comprising complementarity determining regions (CDRs) comprising SEQ ID NOs: 12, 13, and 14 and a heavy chain variable domain comprising CDRs comprising SEQ ID NOs: 15, 16, and 17.
2. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antibody is a single chain variable fragment (scFv) antibody or a single chain Fab fragment (scFab) antibody.
3. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antigen binding fragment is selected from a Fab fragment, a Fab′ fragment, and an Fv fragment.
4. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antibody is a humanized antibody or a chimeric antibody.
5. The antibody or antigen binding fragment thereof according to claim 1 , wherein the light chain variable domain comprises an amino acid sequence that is at least 70% identical to SEQ ID NO: 30 and/or wherein the heavy chain variable domain comprises an amino acid sequence that is at least 70% identical to SEQ ID NO: 31.
6. The antibody or antigen binding fragment thereof according to claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 30 and/or wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 31.
7. The antibody or antigen binding fragment thereof according to claim 1 , wherein the CD133 polypeptide is a human CD133 polypeptide.
8. The antibody or antigen binding fragment thereof according to claim 7 , wherein the human CD133 polypeptide comprises SEQ ID NO: 1.
9. The antibody or antigen binding fragment thereof according to claim 1 , wherein the CD133 polypeptide is denatured.
10. The antibody or antigen binding fragment thereof according to claim 1 , wherein the CD133 polypeptide is on the surface of a cell.
11. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antibody or antigen binding fragment thereof comprises human constant regions.
12. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antibody is an IgG antibody.
13. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antibody is an IgA1, IgA2, IgD, IgG1, IgG2, IgG3, IgG4, IgE or IgM antibody.
14. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antibody is a bispecific antibody.
15. The antibody or antigen binding fragment thereof according to claim 14 , wherein said bispecific antibody binds to a CD3 polypeptide.
16. The antibody or antigen binding fragment thereof according to claim 14 , wherein said bispecific antibody comprises:
(a) a polypeptide comprising SEQ ID NO: 22 and a polypeptide comprising SEQ ID NO: 23;
(b) a polypeptide comprising SEQ ID NO: 24 and a polypeptide comprising SEQ ID NO: 25;
(c) a polypeptide comprising SEQ ID NO: 26; or
(d) a polypeptide comprising SEQ ID NO: 27.
17. A chimeric antigen receptor (CAR) that specifically binds to a CD133 polypeptide, wherein said CAR comprises an extracellular antigen binding domain comprising the antibody or antigen binding fragment thereof according to claim 1 .
18. The antibody or antigen binding fragment thereof according to claim 1 , wherein said antibody or antigen binding fragment thereof is detectably labeled.
19. An immunoconjugate comprising the antibody or antigen binding fragment thereof according to claim 1 and an effector agent.
20. The immunoconjugate according to claim 19 , wherein said effector agent is an anti-neoplastic agent or a toxin.
21. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 1 and a carrier.
22. A method for treating cancer expressing CD133 in a subject, said method comprising administering to the subject an effective amount of the antibody or antigen binding fragment thereof according to claim 1 .
23. The method according to claim 22 , wherein said cancer is selected from a metastatic melanoma, a brain cancer, a prostate cancer, a pancreatic cancer, and a colon cancer.
24. The method according to claim 23 , wherein said brain cancer is a glioblastoma or a medulloblastoma.
25. A method for treating cancer expressing CD133 in a subject, said method comprising administering to the subject an effective amount of the bispecific antibody according to claim 15 .
26. A method for treating cancer expressing CD133 in a subject, said method comprising administering to the subject an effective amount of T cells expressing a CAR according to claim 17 .
27. A method for detecting CD133 and/or quantifying the levels of CD133 expressed by cells, said method comprising contacting a sample suspected of comprising CD133 or cells expressing CD133 with the antibody or antigen binding fragment thereof according to claim 1 .