Means and methods for counteracting myeloproliferative or lymphoproliferative disorders

Abstract

The invention provides human AML-specific binding compounds that are able to bind a cell surface component of AML cells. Therapeutic uses of binding compounds against AML are also provided.

1 . An antibody, or a functional part thereof:
 wherein said antibody, or functional part thereof is able to bind a cell surface component of acute myeloid leukemia (AML) cells, and   wherein said cell surface component is snRNP200.   
     
     
         2 . The antibody or functional part thereof of  claim 1 , wherein said antibody or functional part thereof is of the IgG isotype, preferably IgG1 or IgG3. 
     
     
         3 . An antibody or functional part thereof comprising:
 a heavy chain CDR1 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 7, 9, 11 and 13; and   a heavy chain CDR2 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 14, 15, 20, 22, 24 and 26; and   a heavy chain CDR3 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 27, 28, 33, 35, 37 and 39; and   a light chain CDR1 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 40, 41, 46, 48, 50 and 52; and   a light chain CDR2 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 53, 54, 59, 61, 63 and 65; and   a light chain CDR3 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 66, 67, 72, 74, 76 and 78;   
       wherein said antibody can bind to AML cells. 
     
     
         4 . The antibody or functional part thereof of  claim 3 , further comprising:
 a heavy chain variable domain sequence having at least 80% sequence identity with a sequence selected from the group consisting of SEQ ID NOs: 79, 80, 85, 87, 89 and 91.   
     
     
         5 . The antibody or functional part thereof of  claim 3 , further comprising:
 a light chain variable domain sequence having at least 80% sequence identity with a sequence selected from the group consisting of SEQ ID NOs: 92, 93, 98, 100, 102 and 104.   
     
     
         6 . The antibody or functional part thereof of  claim 1 ,
 wherein said antibody or functional part thereof is coupled to another compound.   
     
     
         7 . The antibody or functional part thereof of  claim 6 ,
 wherein said other compound is a detectable label, a chemotherapeutic drug, a toxic moiety, an immunomodulatory molecule, another AML-specific binding compound, a CD3-specific binding compound, or a radioactive compound.   
     
     
         8 . The antibody or functional part thereof of  claim 1 , further comprising:
 at least one non-natural mutation in a framework region or constant region.   
     
     
         9 . The antibody or functional part thereof of  claim 1 ,
 wherein said functional part is a single domain antibody, a single chain antibody, a nanobody, an unibody, a single chain variable fragment (scFv), a Fab fragment, or a F(ab′)2 fragment.   
     
     
         10 . A bispecific or multispecific binding compound:
 wherein said bispecific or multispecific binding compound can bind to AML cells, and   wherein said bispecific or multispecific binding compound comprises the antibody or functional part thereof of  claim 1 .   
     
     
         11 . A bispecific or multispecific binding compound comprising:
 a heavy chain CDR1 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 7, 9, 11 and 13; and   a heavy chain CDR2 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 14, 15, 20, 22, 24 and 26; and   a heavy chain CDR3 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 27, 28, 33, 35, 37 and 39; and   a light chain CDR1 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 40, 41, 46, 48, 50 and 52; and   a light chain CDR2 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 53, 54, 59, 61, 63 and 65; and   a light chain CDR3 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 66, 67, 72, 74, 76 and 78;   
       wherein said bispecific or multispecific binding compound can bind to AML cells. 
     
     
         12 . The bispecific or multispecific binding compound of  claim 11 , further comprising:
 an immunomodulatory molecule, preferably a CD3-specific binding compound.   
     
     
         13 . A synthetic or recombinant antibody or immunoglobulin comprising:
 one Fab fragment of an antibody or functional part of  claim 3 , and   one Fab fragment of another antibody;   
       wherein said synthetic or recombinant antibody or immunoglobulin can bind to AML, cells. 
     
     
         14 . A chimeric antigen receptor (CAR) T cell comprising:
 a heavy chain CDR1 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 1, 2, 7, 9, 11 and 13; and   a heavy chain CDR2 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 14, 15, 20, 22, 24 and 26; and   a heavy chain CDR3 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 27, 28, 33, 35, 37 and 39; and   a light chain CDR1 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 40, 41, 46, 48, 50 and 52; and   a light chain CDR2 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 53, 54, 59, 61, 63 and 65; and   a light chain CDR3 sequence comprising a sequence selected from the group consisting of SEQ ID NOs: 66, 67, 72, 74, 76 and 78;   
       wherein said chimeric antigen receptor (CAR) T cell can bind AML cells, said CAR T cell. 
     
     
         15 . A synthetic or recombinant nucleic acid molecule or a functional equivalent thereof:
 wherein said synthetic or recombinant nucleic acid molecule or a functional equivalent thereof encodes at least one CDR sequence, or at least the heavy chain variable region or at least the light chain variable region, of an antibody or functional part thereof of  claim 3 .   
     
     
         16 . A vector comprising:
 the nucleic acid molecule or functional equivalent of  claim 15 .   
     
     
         17 . An isolated or recombinant cell, or a non-human animal, comprising:
 an antibody or functional part thereof of  claim 3 .   
     
     
         18 . A composition comprising:
 an antibody or functional part thereof of  claim 3 .   
     
     
         19 . The composition of  claim 18 ,
 wherein said composition is a pharmaceutical composition which comprises a pharmaceutically acceptable carrier, diluent or excipient.   
     
     
         20 . The composition of  claim 18 , further comprising:
 at least two antibodies, or functional parts.   
     
     
         21 . The composition of  claim 18 :
 wherein said composition is a medicament or prophylactic agent.   
     
     
         22 . The composition of  claim 18 :
 wherein said composition is for use in a method for at least in part treating or preventing a myeloproliferative or lymphoproliferative disorder.   
     
     
         23 . The composition of  claim 18 :
 wherein said composition is for use in diagnosis of a myeloproliferative or lymphoproliferative disorder.   
     
     
         24 . The composition of  claim 22 :
 wherein said myeloproliferative disorder is acute myeloid leukemia (AML) or, wherein said lymphoproliferative disorder is lymphoma, B-non-Hodgkin lymphoma or multiple myeloma.   
     
     
         25 . The composition of  claim 18 :
 wherein said composition is used for determining whether a sample comprises myeloproliferative or lymphoproliferative cells.   
     
     
         26 . A method for producing the antibody or functional part thereof of  claim 3 , the method comprising:
 providing a cell with a nucleic acid molecule or functional equivalent;   encoding the antibody or functional part thereof of  claim 3 , and allowing said cell to translate said nucleic acid molecule or functional equivalent, thereby producing said antibody or functional part thereof of  claim 3 , the method preferably further comprising harvesting, purifying and/or isolating said antibody or functional part thereof of  claim 3 .   
     
     
         27 . A method for determining whether a myeloid cell or lymphoid cell is a myeloproliferative cell or lymphoproliferative cell, the method comprising:
 determining whether snRNP200 is present on the surface of said cell, wherein the presence of snRNP200 on the surface of said cell indicates that said cell is myeloproliferative or lymphoproliferative.   
     
     
         28 . A method for identifying myeloproliferative or lymphoproliferative cells, comprising:
 detecting the presence of snRNP200 on the surface of said cells.   
     
     
         29 . A method for determining whether myeloproliferative or lymphoproliferative cells are present in a sample comprising:
 contacting said sample with an antibody or functional part of  claim 3 , and   allowing said antibody or functional part to bind myeloproliferative cells or lymphoproliferative cells, if present, and   determining whether or not myeloproliferative cells or lymphoproliferative cells are bound to said antibody or functional part, thereby determining whether or not myeloproliferative cells or lymphoproliferative cells are present in said sample.   
     
     
         30 . A method for treating or preventing a myeloproliferative or lymphoproliferative disorder, comprising:
 administering to an individual in need thereof a therapeutically effective amount of an antibody or functional part of  claim 3 .   
     
     
         31 . A method for determining whether an individual is suffering from a myeloproliferative or lymphoproliferative disorder, comprising:
 contacting a sample from said individual with an antibody or functional part of  claim 3 , and   allowing said antibody or functional part to bind myeloproliferative cells or lymphoproliferative cells, if present, and   determining whether or not myeloproliferative cells or lymphoproliferative cells are bound to said antibody or functional part, thereby determining whether or nor said individual is suffering from a myeloproliferative disorder or a lymphoproliferative disorder.   
     
     
         32 . A method for determining whether an individual is suffering from a myeloproliferative or lymphoproliferative disorder, comprising:
 determining whether a sample from said individual comprises antibodies that are specific for snRNP200.   
     
     
         33 . A method for typing a myeloid cell-containing sample or a lymphoid cell-containing sample of an individual, the method comprising:
 determining whether snRNP200 is present on the surface of cells in said sample.   
     
     
         34 . A method for determining whether a patient suffering from a myeloproliferative or lymphoproliferative disorder has an improved chance of a positive outcome of treatment with the antibody or functional part thereof of  claim 1 , as compared to the mean population of patients suffering from a myeloproliferative or lymphoproliferative disorder, the method comprising:
 determining whether snRNP200 is present on the surface of myeloproliferative cells or lymphoproliferative cells of said patient.   
     
     
         35 . A method for determining whether a patient suffering from a myeloproliferative disorder or lymphoproliferative disorder is a candidate for treatment with antibody AT12-023, AT12-025, AT13-031, AT13-033, AT13-035 or AT13-037, or a functional part thereof, the method comprising:
 determining whether snRNP200 is present on the surface of myeloproliferative cells or lymphoproliferative cells of said patient.