Compositions and methods for the therapy and diagnosis of prostate cancer

Abstract

Compositions and methods for the therapy and diagnosis of cancer, particularly prostate cancer, are disclosed. Illustrative compositions comprise one or more prostate-specific 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 prostate cancer.

1 .- 22 . (canceled) 
     
     
         23 . An isolated polynucleotide comprising a sequence selected from the group consisting of:
 (a) a sequence recited in SEQ ID NOs: 1-111, 115-171, 173-175, 177, 179-305, 307-315, 326, 328, 330, 332-335, 340-375, 381, 382 and 384-476, 524, 526, 530, 531, 533, 535, 536, 552, 569-572, 587, 591, 593-606, 618-705, 709-774, 777, 789, 817, 823, 824, 878, 880-882, 894, 896, 907, 908, 916-919, 929-931, 938, 939, 942, 944, 945, 948, 967, 969-976, 991, 993-1002, 1004, 1006, 1007, 1010, 1013-1019, 1021, 1023-1027, 1034-1036 and 1038;   (b) a sequence having of at least 20 contiguous residues of a sequence recited in (a);   (c) a sequence having at least 90% identity to a sequence recited in (a);   (d) a sequence complementary to a sequence recited in (a); and   (e) a degenerate variant of a sequence recited in (a).   
     
     
         24 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
 (a) a sequence encoded by a polynucleotide of  claim 23 ;   (b) a sequence recited in SEQ ID NOs: 112-114, 172, 176, 178, 327, 329, 331, 336, 339, 376-380, 383, 477-483, 496, 504, 505, 519, 520, 522, 525, 527, 532, 534, 537-551, 553-568, 573-586, 588-590, 592, 706-708, 775, 776, 778, 780, 781, 811, 814, 818, 826, 827, 853, 855, 858, 860-862, 866-877, 879, 883-893, 895, 897, 898, 909-915, 920-928, 932-934, 940, 941, 943, 946, 947, 949-966, 968, 977-990, 992, 1003, 1005, 1008, 1009, 1011, 1012, 1020, 1022, 1028-1029, 1030-1033 and 1037;   (c) a sequence having at least 20 contiguous residues of a sequence recited in (b); and   (d) a sequence having at least 90% identity to a sequence recited in (b).   
     
     
         25 . An expression vector comprising a polynucleotide of  claim 23  operably linked to an expression control sequence. 
     
     
         26 . A host cell transformed or transfected with an expression vector according to  claim 25 . 
     
     
         27 . An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a polypeptide of  claim 24 . 
     
     
         28 . 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 24 ;   (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.   
     
     
         29 . A fusion protein comprising at least one polypeptide according to  claim 24 . 
     
     
         30 . An oligonucleotide that hybridizes to a polynucleotide of  claim 23  under highly stringent conditions. 
     
     
         31 . 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) a polypeptide according to  claim 24 ;   (b) a polynucleotide according to  claim 23 ; and   (c) an antigen-presenting cell that expresses a polynucleotide according to  claim 23 ,   under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.   
     
     
         32 . An isolated T cell population, comprising T cells prepared according to the method of  claim 31 . 
     
     
         33 . 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) a polypeptide according to  claim 24 ;   (b) a polynucleotide according to  claim 23 ;   (c) an antibody according to  claim 27 ;   (d) a fusion protein according to  claim 29 ;   (e) a T cell population according to  claim 32 ; and   (f) an antigen presenting cell that expresses a polypeptide according to  claim 24 .   
     
     
         34 . A method for stimulating an immune response in a patient, comprising administering to the patient a composition of  claim 33 . 
     
     
         35 . A method for the treatment of a prostate cancer in a patient, comprising administering to the patient a composition of  claim 33 . 
     
     
         36 . 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 31 ;   (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.   
     
     
         37 . A diagnostic kit comprising at least one oligonucleotide according to  claim 30 . 
     
     
         38 . A diagnostic kit comprising at least one antibody according to  claim 27  and a detection reagent, wherein the detection reagent comprises a reporter group. 
     
     
         39 . A method for the treatment of prostate 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) a polypeptide according to  claim 24 ; (ii) a polynucleotide according to  claim 23 ; and (iii) an antigen presenting cell that expresses a polypeptide of  claim 24 , 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.