Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis, and metastasis
The present disclosure provides methodology and compositions for preventing and treating various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, by using an inhibitor of processed forms of lysyl oxidase or lysyl oxidase-like proteins, an inhibitor of LOX or LOXL, or a synergistic combination thereof combined with other therapeutic agents. Methods and compositions for diagnosing or monitoring various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, are also provided. Also provided herein are methods and related compositions, medical devices, systems and kits for preventing or treating various diseases and conditions associated with fibrosis with compositions comprising inhibitors of LOX or LOXL.
1. A method of treating cancer, comprising:
administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to SEQ ID NO: 3, 7, 11, or 16.
2. The method of claim 1 , wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.
3. The method of claim 1 , wherein the antibody or fragment thereof is humanized or human.
4. The method of claim 1 , further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.
5. The method of claim 1 , wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.
6. The method of claim 1 , wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.
7. The method of claim 1 , wherein the cancer is a pancreatic cancer.
8. The method of claim 1 , wherein the cancer is liver cancer.
9. The method of claim 1 , wherein the cancer is lung cancer.
10. The method of claim 1 , wherein the antibody or fragment thereof specifically binds to SEQ ID NO: 3.
11. The method of claim 1 , wherein the antibody or fragment thereof specifically binds to SEQ ID NO: 7.
12. The method of claim 1 , wherein the antibody or fragment thereof specifically binds to SEQ ID NO: 11.
13. The method of claim 1 , wherein the antibody or fragment thereof specifically binds to SEQ ID NO: 16.
14. A method of treating cancer, comprising:
administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to a peptide consisting of SEQ ID NO: 3, SEQ ID NO: 7, SEQ ID NO: 11, or SEQ ID NO: 16.
15. The method of claim 14 , wherein the peptide consists of SEQ ID NO: 3.
16. The method of claim 14 , wherein the peptide consists of SEQ ID NO: 7.
17. The method of claim 14 , wherein the peptide consists of SEQ ID NO: 11.
18. The method of claim 14 , wherein the peptide consists of SEQ ID NO: 16.
19. The method of claim 14 , wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.
20. The method of claim 14 , wherein the antibody or fragment thereof is humanized or human.
21. The method of claim 14 , further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.
22. The method of claim 14 , wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.
23. The method of claim 14 , wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.
24. The method of claim 14 wherein the cancer is a pancreatic cancer.
25. The method of claim 14 , wherein the cancer is liver cancer.
26. The method of claim 14 , wherein the cancer is lung cancer.
27. A method of treating cancer, comprising:
administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to SEQ ID NO: 5.
28. The method of claim 27 , wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.
29. The method of claim 27 , wherein the antibody or fragment thereof is humanized or human.
30. The method of claim 27 , further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.
31. The method of claim 27 , wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.
32. The method of claim 27 , wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.
33. The method of claim 27 , wherein the cancer is a pancreatic cancer.
34. The method of claim 27 , wherein the cancer is liver cancer.
35. The method of claim 27 , wherein the cancer is lung cancer.
36. A method of treating cancer, comprising:
administering to a human in need thereof a monoclonal anti-LOXL2 antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof specifically binds to a peptide consisting of SEQ ID NO: 5.
37. The method of claim 36 , wherein the administration inhibits or reduces tumor growth, invasion, or metastasis in the human.
38. The method of claim 36 , wherein the antibody or fragment thereof is humanized or human.
39. The method of claim 36 , further comprising administering to the human an anti-neoplastic agent, a chemotherapeutic agent, an anti-angiogenic agent, or an anti-fibrotic agent.
40. The method of claim 36 , wherein the cancer is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, skin cancer, bone cancer, ovarian cancer, liver cancer, anal cancer, bile duct cancer, esophageal cancer, leukemia, lymphoma, bladder cancer, uterine cancer, brain cancer, kidney cancer, cancer of the head and neck, cancer of the stomach, myeloma, testicular cancer, germ cell tumor, neuroendocrine tumor, cervical cancer, and gastrointestinal cancer.
41. The method of claim 36 , wherein the cancer is selected from the group consisting of pancreatic, liver, and lung cancers.
42. The method of claim 36 , wherein the cancer is a pancreatic cancer.
43. The method of claim 36 , wherein the cancer is liver cancer.
44. The method of claim 36 , wherein the cancer is lung cancer.