A compound that specifically binds to kir3dl2 for use in the treatment of peripheral t cell lymphoma

Abstract

The present disclosure relates to methods for the treatment, prevention and diagnostic of peripheral T cell lymphoma using compounds that specifically bind KIR3DL2. The disclosure also relates to use of antibodies that specifically bind KIR3DL2 in diagnostic and theranostic assays in the detection and treatment of peripheral T cell lymphoma.

1 - 36 . (canceled) 
     
     
         37 . A method of treating an adult T cell leukemia (ATL), comprising administering to the individual a therapeutically active amount of a compound that binds a KIR3DL2 polypeptide and depletes KIR3DL2-expressing tumor cells. 
     
     
         38 . The method of  claim 37 , wherein the ATL is an HTLV+ATL. 
     
     
         39 . The method of  claim 37 , wherein the treatment comprises:
 a) determining the KIR3DL2 polypeptide status of malignant cells within the individual having an ATL, and   b) upon a determination that the individual has KIR3DL2 polypeptide prominently expressed on the surface of malignant cells, administering to the individual said compound that binds a KIR3DL2 polypeptide.   
     
     
         40 . The method of  claim 37 , wherein the compound that binds a KIR3DL2 polypeptide is an anti-KIR3DL2 antibody. 
     
     
         41 . The method of  claim 40 , wherein the antibody comprises an amino acid modification that enhances binding to a human Fey receptor. 
     
     
         42 . The method of  claim 40 , wherein the antibody is linked to a toxic agent. 
     
     
         43 . The method of  claim 40 , wherein the anti-KIR3DL2 antibody binds human KIR3DL2 but does not bind to human KIR3DL1. 
     
     
         44 . The method of  claim 40 , wherein the anti-KIR3DL2 antibody has reduced binding to a KIR3DL2 polypeptide having a mutation at residue P179 and/or residue S181, compared to a wild-type KIR3DL2 polypeptide of SEQ ID NO: 1. 
     
     
         45 . The method of  claim 40 , wherein the anti-KIR3DL2 antibody has reduced binding to a KIR3DL2 polypeptide having a mutation at residue 160 and/or residue G62, compared to a wild-type KIR3DL2 polypeptide of SEQ ID NO: 1. 
     
     
         46 . The method of  claim 40 , wherein the anti-KIR3DL2 antibody binds the same epitope on KIR3DL2 as antibodies AZ158, 19H12, 2B12 or 12B11. 
     
     
         47 . A method for diagnosing or monitoring an adult T cell leukemia (ATL) in an individual, the method comprising obtaining from an individual a biological sample that comprises ATL cells, bringing said cells into contact with an antibody that binds a human KIR3DL2 polypeptide, and detecting cells that express KIR3DL2. 
     
     
         48 . The method of  claim 47 , wherein the antibody that binds a KIR3DL2 polypeptide is an antibody that binds a human KIR3DL2 polypeptide but does not bind to a human KIR3DL1 polypeptide. 
     
     
         49 . The method of  claim 47 , wherein the antibody that binds a KIR3DL2 polypeptide competes with antibody 12B11 for binding to a human KIR3DL2 polypeptide. 
     
     
         50 . A method for determining whether a KIR3DL2 polypeptide is expressed on the surface of a cell, the method comprising obtaining from an individual a biological sample that comprises cells, bringing said cells into contact with an antibody that competes with antibody 19B12 for binding to a human KIR3DL2 polypeptide, and detecting cells that express KIR3DL2 using flow cytometry. 
     
     
         51 . The method of  claim 50 , wherein the cells are tumor cells. 
     
     
         52 . The method of  claim 51 , wherein the tumor cells are ATL cells.