Compositions and methods for the therapy and diagnosis of breast cancer

Abstract

Compositions and methods for the therapy and diagnosis of cancer, particularly breast cancer, are disclosed. Illustrative compositions comprise one or more breast tumor polypeptides, immunogenic portions thereof, polynucleotides that encode such polypeptides, antigen presenting cell that expresses such polypeptides, and T cells that are specific for cells expressing such polypeptides. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases, particularly breast cancer.

What is claimed:  
     
         1 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 (a) sequences provided in SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300;    (b) complements of the sequences provided in SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300;    (c) sequences consisting of at least 20 contiguous residues of a sequence provided in SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300;    (d) sequences that hybridize to a sequence provided in SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300, under moderately stringent conditions;    (e) sequences having at least 75% identity to a sequence of SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300;    (f) sequences having at least 90% identity to a sequence of SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300; and    (g) degenerate variants of a sequence provided in SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300.    
     
     
         2 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) sequences provided in SEQ ID NO: 39-41, 206, 208, 209, 294, 295 and 301;    (b) sequences encoded by a polynucleotide of    claim 1   ;    (c) sequences having at least 70% identity to a sequence encoded by a polynucleotide of    claim 1   ; and    (d) 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 . An oligonucleotide that hybridizes to a sequence recited in SEQ ID NO: 1-38, 42-204, 205, 207, 210-290, 293, 296, 297 and 300 under moderately stringent conditions.  
     
     
         9 . 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 2   , under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.    
     
     
         10 . An isolated T cell population, comprising T cells prepared according to the method of    claim 9   .  
     
     
         11 . 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 10   ; and    (f) antigen presenting cells that express a polypeptide according to    claim 2   .    
     
     
         12 . A method for stimulating an immune response in a patient, comprising administering to the patient a composition of    claim 11   .  
     
     
         13 . A method for the treatment of a cancer in a patient, comprising administering to the patient a composition of    claim 11   .  
     
     
         14 . 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 8   ;    (c) detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; and    (d) compare 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.    
     
     
         15 . A diagnostic kit comprising at least one oligonucleotide according to    claim 8   .  
     
     
         16 . A diagnostic kit comprising at least one antibody according to    claim 5    and a detection reagent, wherein the detection reagent comprises a reporter group.  
     
     
         17 . 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.