Antibodies that bind to lysyl oxidase-like 2 (loxl2) and methods of use therefor

Abstract

The present disclosure provides lysyl oxidase-like-2 (LOXL2) polypeptide binding agents, including, for example, antibodies that specifically bind a LOXL2 polypeptide; and further provides compositions comprising same. The binding agents can be used in various treatment and diagnostic methods, which are also provided.

What is claimed is: 
     
         1 . An isolated antibody to lysyl oxidase-like-2 (LOXL2) that specifically binds to an epitope defined by amino acids 325 through 434 of the sequence depicted in  FIG. 1  and set forth in SEQ ID NO:1. 
     
     
         2 . The antibody of  claim 1 , wherein the epitope comprises amino acids within the sequence TPAMGLQKK (SEQ ID NO:2). 
     
     
         3 . The isolated antibody of  claim 1 , wherein the antibody inhibits enzymatic activity of a LOXL2 polypeptide. 
     
     
         4 . The isolated antibody of  claim 1 , wherein the antibody does not inhibit enzymatic activity of a LOXL2 polypeptide. 
     
     
         5 . The isolated antibody of  claim 1 , wherein the antibody binds the epitope with an affinity of from about 10 7  M −1  to about 10 12  M −1 . 
     
     
         6 . The isolated antibody of  claim 1 , wherein the antibody comprises a heavy chain, and wherein the heavy chain of the antibody is of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         7 . The isolated antibody of  claim 1 , wherein the binding agent is detectably labeled. 
     
     
         8 . The isolated antibody of  claim 1 , wherein the antibody is a Fv, scFv, Fab, F(ab′)2, or Fab′. 
     
     
         9 . The isolated antibody of  claim 1 , wherein the antibody is humanized. 
     
     
         10 . The isolated antibody of  claim 1 , wherein the antibody is chimeric. 
     
     
         11 . The isolated antibody of  claim 1 , wherein the antibody comprises a covalently linked moiety selected from the group consisting of a non-peptide synthetic polymer, a lipid, a fatty acid, a polysaccharide, a carbohydrate, or a contrast agent. 
     
     
         12 . The isolated antibody of  claim 11 , wherein the synthetic polymer is poly(ethylene glycol) polymer. 
     
     
         13 . The isolated antibody of  claim 1 , wherein the antibody is immobilized on a solid support. 
     
     
         14 . The isolated antibody of  claim 1 , wherein the antibody comprises a cancer chemotherapeutic agent covalently or non-covalently linked to the antibody. 
     
     
         15 . A kit for treating a condition associated with LOXL2 comprising
 a composition comprising an isolated LOXL2 binding agent of  claim 1  and   a pharmaceutically acceptable carrier or excipient.   
     
     
         16 . The kit of  claim 15 , wherein said condition associated with LOXL2 is a tumor, a metastasis, angiogenesis, or fibrosis. 
     
     
         17 . The kit of  claim 15 , wherein the LOXL2 binding agent comprises a detectable label, a therapeutic agent or both. 
     
     
         18 . A method of diagnosing a condition associated with LOXL2 comprising:
 assessing a level of LOXL2 in a sample of a subject by contacting said sample with an isolated antibody according to  claim 1 ,   wherein a change in level of LOXL2 in the sample in comparison with a reference sample indicates the presence of the condition associated with LOXL2.   
     
     
         19 . The method of  claim 18 , wherein said condition associated with LOXL2 is a tumor, a metastasis, angiogenesis, or fibrosis. 
     
     
         20 . The method of  claim 19 , wherein an increase in LOXL2 levels in the sample in comparison with a reference sample indicates the presence of a tumor or metastasis thereof, or an increase in tumor or metastatic growth. 
     
     
         21 . The method of  claim 20 , wherein the reference sample is a sample taken from the subject at an earlier time point or from unaffected tissue of the same type, or is a sample from another individual. 
     
     
         22 . The method of  claim 18 , wherein the antibody is detectably labeled. 
     
     
         23 . A method of inhibiting LOXL2 activity by contacting a sample or a cellular tissue with an isolated antibody according to  claim 1 . 
     
     
         24 . The method of  claim 23 , wherein contacting occurs in vitro or ex vivo. 
     
     
         25 . The method of  claim 23 , wherein contacting occurs in vivo. 
     
     
         26 . The method of  claim 23 , wherein inhibiting LOXL2 reduces a condition in a subject selected from the group consisting of tumor growth, angiogenesis, and fibrosis. 
     
     
         27 . A method of reducing growth of a tumor in a subject, comprising administering the antibody of  claim 1  to the subject. 
     
     
         28 . The method of  claim 27 , wherein said tumor is a primary tumor or a metastatic tumor. 
     
     
         29 . The method of  claim 27 , wherein said tumor is a solid tumor. 
     
     
         30 . A method of inhibiting angiogenesis in a subject comprising administering the antibody of  claim 1  to the subject. 
     
     
         31 . A method of inhibiting a fibrotic disease in a subject by administering the antibody of  claim 1  to the subject. 
     
     
         32 . A method of monitoring a subject's response to an anti-LOXL2 therapy by detecting LOXL2 levels and/or activity using an antibody according to  claim 1 .