Recombinant egfl7, egfl7 antibodies, and uses thereof

Abstract

The present disclosure relates to recombinant EGFL7, EGFL7 antibodies, and uses thereof.

We claim: 
     
         1 . A method for treating acute myeloid leukemia (AML), comprising:
 administering to a subject in need thereof an effective amount of an antibody or antigen-binding fragment thereof that specifically binds to an EGFL7 polypeptide.   
     
     
         2 . The method of  claim 1 , wherein the antibody or antigen-binding fragment thereof binds to the EGF/DSL domain of EGFL7. 
     
     
         3 . The method of any one of  claim 1  or  2 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein the antibody or antigen-binding fragment thereof is parsatuzumab. 
     
     
         5 . The method of any one of  claims 1  to  4 , wherein the antibody or antigen-binding fragment thereof is administered in combination with an NP-antagomiR-126 therapy. 
     
     
         6 . The method of any one of  claims 1  to  5 , wherein the antibody or antigen-binding fragment thereof is administered in combination with an additional chemotherapeutic agent. 
     
     
         7 . The method of  claim 6 , wherein the additional chemotherapeutic agent is selected from cytarabine, daunorubicin, idarubicin, mitoxantrone, vincristine, Cladribine (Leustatin®, 2-CdA), Fludarabine (Fludara®), Topotecan, Etoposide (VP-16), 6-thioguanine (6-TG), Hydroxyurea (Hydrea®), Corticosteroid drugs, such as prednisone or dexamethasone (Decadron®), Methotrexate (MTX), 6-mercaptopurine (6-MP), Azacitidine (Vidaza®), or Decitabine (Dacogen®). 
     
     
         8 . The method of  claim 6  or  7 , wherein the additional chemotherapeutic agent is a FLT3 inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the FLT3 inhibitor is gilteritinib. 
     
     
         10 . The method of any one of  claims 1  to  9 , wherein the acute myeloid leukemia (AML) is cytogenetically normal acute myeloid leukemia (CN-AML). 
     
     
         11 . The method of any one of  claims 1  to  10 , wherein the antibody or antigen-binding fragment thereof inhibits EGFL7 activity in acute myeloid leukemia blasts. 
     
     
         12 . A method of predicting responsiveness of a subject with acute myeloid leukemia to an EGFL7 inhibitor, the method comprising:
 assaying a sample from the subject for the expression of EGFL7; and   comparing the expression of EGFL7 to a healthy control;   wherein an increase in EGFL7 expression in the sample compared to the healthy control is an indication of responsiveness of the subject to the EGFL7 inhibitor.   
     
     
         13 . The method of  claim 12 , wherein the expression of EGFL7 is detected by measuring EGFL7 protein levels. 
     
     
         14 . The method of  claim 12 , wherein the expression of EGFL7 is detected by measuring EGFL7 mRNA levels. 
     
     
         15 . The method of any one of  claims 12  to  14 , wherein the EGFL7 expression in the sample is increased at least 10% relative to a healthy control. 
     
     
         16 . The method of any one of  claims 12  to  15 , wherein the method further comprises treating the subject with an EGFL7 inhibitor if an increase in EGFL7 expression is detected. 
     
     
         17 . The method of  claim 16 , wherein the EGFL7 inhibitor is an antibody or antigen-binding fragment thereof that specifically binds to an EGFL7 polypeptide. 
     
     
         18 . The method of  claim 17 , wherein the antibody or antigen-binding fragment thereof binds to the EGF/DSL domain of EGFL7. 
     
     
         19 . The method of  claim 17 , wherein the antibody is a monoclonal antibody. 
     
     
         20 . The method of  claim 17 , wherein the antibody is parsatuzumab. 
     
     
         21 . The method of any one of  claims 16  to  20 , wherein the antibody or antigen-binding fragment thereof is administered in combination with an NP-antagomiR-126 therapy. 
     
     
         22 . The method of any one of  claims 16  to  21 , wherein the antibody or antigen-binding fragment thereof is administered in combination with an additional chemotherapeutic agent. 
     
     
         23 . The method of  claim 22 , wherein the additional chemotherapeutic agent is selected from cytarabine, daunorubicin, idarubicin, mitoxantrone, vincristine, Cladribine (Leustatin®, 2-CdA), Fludarabine (Fludara®), Topotecan, Etoposide (VP-16), 6-thioguanine (6-TG), Hydroxyurea (Hydrea®), Corticosteroid drugs, such as prednisone or dexamethasone (Decadron®), Methotrexate (MTX), 6-mercaptopurine (6-MP), Azacitidine (Vidaza®), or Decitabine (Dacogen®). 
     
     
         24 . The method of  claim 22  or  23 , wherein the additional chemotherapeutic agent is a FLT3 inhibitor. 
     
     
         25 . The method of  claim 24 , wherein the FLT3 inhibitor is gilteritinib. 
     
     
         26 . The method of any one of  claims 12  to  25 , wherein the acute myeloid leukemia (AML) is cytogenetically normal acute myeloid leukemia (CN-AML). 
     
     
         27 . A method of expanding hematopoietic stem and progenitor cells (HSPCs) comprising: administering to a hematopoietic stem and progenitor cell a recombinant EGFL7 protein. 
     
     
         28 . The method of  claim 27 , wherein the recombinant EGFL7 protein does not cause a loss of stem cell potential. 
     
     
         29 . The method of  claim 27  or  28 , wherein the hematopoietic stem and progenitor cells (HSPCs) are selected from HSC, MPP1-4, CMP, GMP, or MEP populations. 
     
     
         30 . A composition comprising: an antibody or antigen-binding fragment thereof that specifically binds to an EGFL7 polypeptide; and a FLT3 inhibitor. 
     
     
         31 . The composition of  claim 30 , wherein the antibody or antigen-binding fragment thereof binds to the EGF/DSL domain of EGFL7. 
     
     
         32 . The composition of  claim 30 , wherein the antibody is a monoclonal antibody. 
     
     
         33 . The composition of  claim 30 , wherein the antibody is parsatuzumab. 
     
     
         34 . The composition of any one of  claims 30  to  33 , wherein the FLT3 inhibitor is gilteritinib.