Evaluating MMP expression in patient stratification and other therapeutic, diagnostic and prognostic methods for cancer
View Patent ↗Provided are compositions, methods and kits for quantifying the expression and/or activity of MMP-14 and other biomarkers of cancer, which may be used diagnostically and prognostically, e.g., in patient stratification and evaluation of appropriate therapeutic regimens.
1. A method of identifying a subject who may benefit from administration of an MMP-14 binding protein to treat cancer, the method comprising evaluating an expressional ratio of MMP-14 to MMP-9, an expressional ratio of MMP-14 to MMP-2, or an expressional ratio of MMP-2 to MMP-9 in a sample from the subject, and if the expressional ratio of MMP-14 to MMP-9, the expressional ratio of MMP-14 to MMP-2, or the expressional ratio of MMP-2 to MMP-9 is greater than 1, identifying the subject for administration of an MMP-14 binding protein.
2. A method of selecting a therapy for cancer for a subject, the method comprising evaluating an expressional ratio of MMP-14, to MMP-9, an expressional ratio of MMP-14 to MMP-2 or an expressional ratio of MMP-2 to MMP-9 in a sample from the subject, and
if the expressional ratio of MMP-14 to MMP-9, the expressional ratio of MMP-14 to MMP-2, or the expressional ratio of MMP-2 to MMP-9 is greater than 1, selecting an MMP-14 binding protein as the cancer therapy.
3. The method of any one of claim 1 or 2 , wherein the cancer is selected from the group consisting of: osteotropic cancer, breast cancer, lung cancer, colon cancer and prostate cancer.
4. The method of claim 3 , wherein the sample is a tumor biopsy.
5. The method of claim 1 or 2 , wherein the expressional ratio is the ratio of MMP-14 to MMP-9 expression or the ratio of MMP-14 to MMP-9 protein activity.
6. The method of claim 1 or 2 , wherein the expressional ratio is the ratio of MMP-14 to MMP-2 expression or the ratio of MMP-14 to MMP-2 protein activity.
7. The method of claim 1 or 2 , wherein the expression ratio is the ratio of MMP-2 to MMP-9 expression or the ratio of MMP-2 to MMP-9 protein activity.
8. The method of claim 1 or 2 , wherein the MMP-14 binding protein is an antibody or antibody fragment.
9. The method of claim 8 , wherein the antibody fragment is a single chain antibody, a Fab fragment, an sFab fragment, a F(ab′) 2 fragment, an Fd fragment, an Fv fragment, an scFv fragment, or a domain antibody (dAb) fragment.
10. The method of claim 8 , wherein the antibody or antibody fragment competes for binding with DX-2400.
11. The method of claim 5 or 6 , wherein the expression is protein expression.
12. The method of claim 11 , wherein the level of protein expression is determined using an MMP-14, MMP-9 and/or MMP-2 antibody.
13. The method of claim 8 , wherein the antibody or antibody fragment is a human antibody, an effectively human antibody or a humanized antibody.
14. The method of claim 1 or 2 , wherein the cancer is melanoma.
15. The method of claim 1 or 2 , wherein the cancer is a diffuse large B-cell lymphoma.
16. The method of claim 1 or 2 , wherein the MMP-14 binding protein comprises heavy chain CDR1, CDR2 and CDR3 of SEQ ID NO: 13 and light chain CDR1, CDR2 and CDR3 of SEQ ID NO:14.
17. The method of claim 16 , wherein the MMP-14 binding protein is DX-2400.
18. The method of claim 16 , wherein the MMP-14 binding protein is M0038-F01.
19. The method of claim 1 or 2 , wherein the MMP-14 binding protein is DX-2410.