Compositions and methods for the detection, diagnosis and therapy of hematological malignancies

Abstract

Disclosed are methods and compositions for the detection, diagnosis, prognosis, and therapy of hematological malignancies, and in particular, B cell leukemias, lymphomas and multiple myelomas. Disclosed are compositions, methods and kits for eliciting immune and T cell responses to specific malignancy-related antigenic polypeptides and antigenic polypeptide fragments thereof in an animal. Also disclosed are compositions and methods for use in the identification of cells and biological samples containing one or more hematological malignancy-related compositions, and methods for the detection and diagnosis of such diseases and affected cell types. Also disclosed are diagnostic and therapeutic kits, as well as methods for the diagnosis, therapy and/or prevention of a variety of leukemias and lymphomas.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 (a) the sequences provided in SEQ ID NOs:10,486-10,536; SEQ ID NOs:10,537-10,580; SEQ ID NOs:10,581-10,596; SEQ ID NO:10,597; SEQ ID NO:10,845; SEQ ID NO:10,846; SEQ ID NO:10,970; SEQ ID NO:10,971; SEQ ID NO:10,972; SEQ ID NO:10,973; and SEQ ID NO:10,974;    (b) complements of any of the sequences provided in SEQ ID NOs:10,486-10,536; SEQ ID NOs:10,537-10,580; SEQ ID NOs:10,581-10,596; SEQ ID NO:10,597; SEQ ID NO:10,845; SEQ ID NO:10,846; SEQ ID NO:10,970; SEQ ID NO:10,971; SEQ ID NO:10,972; SEQ ID NO:10,973; and SEQ ID NO:10,974;    (c) sequences having at least 90% identity to any one of the sequences provided in SEQ ID NOs:10,486-10,536; SEQ ID NOs:10,537-10,580; SEQ ID NOs:10,581-10,596; SEQ ID NO:10,597; SEQ ID NO:10,845; SEQ ID NO:10,846; SEQ ID NO:10,970; SEQ ID NO:10,971; SEQ ID NO:10,972; SEQ ID NO:10,973; and SEQ ID NO:10,974; and    (d) degenerate variants of any one of the sequences provided in SEQ ID NOs:10,486-10,536; SEQ ID NOs:10,537-10,580; SEQ ID NOs:10,581-10,596; SEQ ID NO:10,597; SEQ ID NO:10,845; SEQ ID NO:10,846; SEQ ID NO:10,970; SEQ ID NO:10,971; SEQ ID NO:10,972; SEQ ID NO:10,973; and SEQ ID NO:10,974.    
     
     
         2  An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences encoded by a polynucleotide of  claim 1;  and  
 (b) sequences having at least 90% identity to a sequence encoded by a polynucleotide of  claim 1 .  
 
     
     
         3 . An expression vector comprising a polynucleotide of  claim 1  operably linked to an expression control sequence.  
     
     
         4 . A host cell transformed or transfected with an expression vector according to  claim 3 .  
     
     
         5 . An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide of  claim 2 .  
     
     
         6 . A method for detecting the presence of a cancer in a patient, comprising the steps of: 
 (a) obtaining a biological sample from the patient;    (b) contacting the biological sample with a binding agent that binds to a polypeptide of  claim 2;     (c) detecting in the sample an amount of polypeptide that binds to the binding agent; and    (d) comparing the amount of polypeptide to a predetermined cut-off value and therefrom determining the presence of a cancer in the patient.    
     
     
         7 . A fusion protein comprising at least one polypeptide according to  claim 2 .  
     
     
         8 . The fusion protein of  claim 7 , further comprising Ra12.  
     
     
         9 . The fusion protein of  claim 7 , further comprising a His tag.  
     
     
         10 . An oligonucleotide that hybridizes to the polynucleotides of  claim 1 .  
     
     
         11 . A method for stimulating and/or expanding T cells specific for a tumor protein, comprising contacting T cells with at least one component selected from the group consisting of: 
 (a) polypeptides according to  claim 2;     (b) polynucleotides according to  claim 1;  and    (c) antigen-presenting cells that express a polypeptide according to  claim 1 , under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.    
     
     
         12 . An isolated T cell population, comprising T cells prepared according to the method of  claim 11 .  
     
     
         13 . A composition comprising a first component selected from the group consisting of physiologically acceptable carriers and immunostimulants, and a second component selected from the group consisting of: 
 (a) polypeptides according to  claim 2;     (b) polynucleotides according to  claim 1;     (c) antibodies according to  claim 5;     (d) fusion proteins according to  claim 7;     (e) T cell populations according to  claim 12;  and    (f) antigen presenting cells that express a polypeptide according to  claim 2 .    
     
     
         14 . A method for stimulating an immune response in a patient, comprising administering to the patient a composition of  claim 13 .  
     
     
         15 . A method for the treatment of a cancer in a patient, comprising administering to the patient a composition of  claim 13 .  
     
     
         16 . A method for determining the presence of a cancer in a patient, comprising the steps of: 
 (a) obtaining a biological sample from the patient;    (b) contacting the biological sample with an oligonucleotide according to  claim 10;     (c) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and    (d) comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value, and therefrom determining the presence of the cancer in the patient.    
     
     
         17 . A diagnostic kit comprising at least one oligonucleotide according to  claim 10 .  
     
     
         18 . A diagnostic kit comprising at least one antibody according to  claim 5  and a detection reagent, wherein the detection reagent comprises a reporter group.  
     
     
         19 . A method for inhibiting the development of a cancer in a patient, comprising the steps of: 
 (a) incubating CD4+ and/or CD8+ T cells isolated from a patient with at least one component selected from the group consisting of: (i) polypeptides according to  claim 2;  (ii) polynucleotides according to  claim 1;  and (iii) antigen presenting cells that express a polypeptide of  claim 2 , such that T cell proliferate;    (b) administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of a cancer in the patient.    
     
     
         20 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 (a) sequence provided in SEQ ID NO:10,469 or SEQ ID NO:10,470;    (b) complements of the sequence provided in SEQ ID NO: 10,469 or SEQ ID NO: 10,470;    (c) sequences having at least 90% identity to SEQ ID NO:10,469 or SEQ ID NO:10,470; and    (d) degenerate variants of SEQ ID NO: 10,469 or SEQ ID NO: 10,470.    
     
     
         21 . An isolated polypeptide comprising an amino acid sequence provided in SEQ ID NO:10,471 or SEQ ID NO:10,474.  
     
     
         22 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 (a) sequence provided in SEQ ID NO:10,480;    (b) complements of the sequence provided in SEQ ID NO: 10,480;    (c) sequences having at least 90% identity to a sequence of SEQ ID NO: 10,480; and    (d) degenerate variants of a sequence provided in SEQ ID NO: 10,480.    
     
     
         23 . An isolated polypeptide comprising an amino acid sequence of SEQ ID NO:10,481.  
     
     
         24 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences encoded by a polynucleotide of  claim 20  or  22 ; and    (b) sequences having at least 90% identity to a sequence encoded by a polynucleotide of  claim 20  or  22 .    
     
     
         25 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences provided in any one of SEQ ID NOs:10,599-10,819; and    (b) sequences provided in anyone of SEQ ID NOs:10,820-10,842.    
     
     
         26 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences provided in any one of SEQ ID NOs: 10,849-10,908; and    (b) sequences provided in any one of SEQ ID NOs:10,909-10,968.