Brachyury polypeptides and methods for use

Abstract

It is disclosed herein that Brachyury is expressed in human tumors, specifically in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testes, as well as in lung, colon and prostate carcinomas. Immunogenic Brachyury polypeptides are disclosed herein. These polypeptides can be used in diagnostic assays for Brachyury expression, as well as for inducing an immune response to Brachyury. Polynucleotides encoding the immunogenic Brachyury polypeptides, vectors including these polypeptides, host cells transformed with these vectors, and methods of using these polypeptides, polynucleotides, vectors, and host cells are provided. Methods of diagnosing a Brachyury-expressing cancer are also provided. Exemplary cancers include small lung, colon, intestine, stomach, kidney, bladder, uterus, ovary, and testes and prostate cancers. Methods of treating cancer are also disclosed.

1 .- 21 . (canceled) 
     
     
         22 . An antisense molecule or an siRNA that specifically binds a nucleotide sequence encoding SEQ ID NO: 1 for use in a method of inhibiting growth or metastasis of a tumor in a subject, comprising
 selecting a subject having the tumor; and   administering a therapeutically effective amount of the antisense molecule or siRNA to the subject having the tumor,   thereby inhibiting growth or metastasis of the tumor in the subject,   wherein the cancer cell is from a cancer of the small intestine, stomach cancer, kidney cancer, bladder cancer, uterine cancer, ovarian cancer, testicular cancer, lung cancer, breast cancer, bronchial tube cancer, colon cancer, prostate cancer, or a B cell tumor.   
     
     
         23 . The antisense molecule of  claim 22 , wherein the cancer cell is from a B cell tumour, wherein the B cell tumor is chronic lymphocytic leukemia. 
     
     
         24 . The antisense molecule or siRNA of  claim 22 , comprising administering to the subject a therapeutically effective amount of an siRNA. 
     
     
         25 . The antisense molecule or siRNA of  claim 22 , further comprising administering to the subject a therapeutically effective amount of an isolated polypeptide comprising at most twelve consecutive amino acids, wherein the isolated polypeptide comprises the amino acid sequence set forth as one of:
 (a) WLLPGTSTX 1  (SEQ ID NO: 3), wherein X 1  is a leucine (L) or a valine (V);   (b) SX 2 YX 3 SLX 4 SX 5  (SEQ ID NO: 18), wherein X 2  and X 5  are either a valine or a leucine, wherein X 3  is proline (P), serine (S), threonine (T), leucine (L), or valine (V) and wherein X 4  is tryptophan (W), valine (V), leucine (L), isoleucine (I), serine (S) or threorine (T);   (c) WLLX 6 GTSTX 7  (SEQ ID NO: 19), wherein X 6  is serine (S), threonine (T), isoleucine (I), valine (V) and wherein X 7  is leucine (L) or valine;   (d) X 8 LIASTTPV (SEQ ID NO: 20, wherein X 8  is one of tyrosine (Y) or tryptophan (W);   (e) X 9 LIASX 10 TPV (SEQ ID NO: 21), wherein X 9  is an arginine (R), tyrosine (Y) or tryptophan (W) and X 10  is a valine (V), lysine (L), isoleucine (I), serine (S) or threonine (T); or   (f) ALYSFLLDFV (SEQ ID NO: 22).