Methods and compositions for treating and diagnosing diseases

Abstract

Methods and compositions for diagnosing and treating diseases, particularly cancer, associated with differential expression of cancer-associated targets (CAT) in disease cells compared to healthy cells are provided. Also provided are antagonists and agonists of CAT, and methods for screening agents that modulate CAT level or activity in vivo or in vitro.

1 . An isolated CAT protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-4, 9, 11-12, 16-19, 24-36, 51-59, 69-74, 81-85, 91-102, 115-116, 119-121, 127-134, 144-145, 148-149, 152-159, 168-174, and 182-183. 
     
     
         2 . A composition comprising the CAT protein of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         3 . An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
 a) SEQ ID NOS:5-8, 10, 13-15, 20-23, 37-50, 60-68, 75-80, 86-90, 103-114, 117-118, 122-126, 135-143, 146-147, 150-151, 160-167, 175-181, 184-185;   b) nucleotide sequences that encode a CAT protein comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-4, 9, 11-12, 16-19, 24-36, 51-59, 69-74, 81-85, 91-102, 115-116, 119-121, 127-134, 144-145, 148-149, 152-159, 168-174, and 182-183; and   c) nucleotide sequences that are completely complementary to the nucleotide sequences of a) or b).   
     
     
         4 . An isolated RNAi or antisense nucleic acid molecule that selectively binds to the nucleic acid molecule of  claim 3 . 
     
     
         5 . An isolated antibody that selectively binds to the CAT protein of  claim 1 . 
     
     
         6 . The antibody of  claim 5 , wherein the antibody is at least one of a monoclonal, polyclonal, fully human, humanized, chimeric, single-chain, or anti-idiotypic antibody. 
     
     
         7 . A cell line, hybridoma, phage, or transgenic organism that produces the antibody of  claim 5 . 
     
     
         8 . The antibody of  claim 5 , wherein the antibody is coupled to a composition selected from the group consisting of detectable substances and therapeutic agents. 
     
     
         9 . A composition comprising the antibody of  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         10 . An isolated antibody fragment of the antibody of  claim 5 , wherein the antibody fragment comprises a fragment selected from the group consisting of:
 a) an Fab fragment;   b) an F(ab′) 2  fragment; and   c) an Fv fragment.   
     
     
         11 . A method of modulating cell proliferation or apoptosis, the method comprising contacting a cell with the antibody of  claim 5 . 
     
     
         12 . The method of  claim 11 , wherein the method comprises either inhibiting proliferation of cancer cells or stimulating apoptosis of cancer cells. 
     
     
         13 . A method of modulating cell proliferation or apoptosis, the method comprising contacting a cell with the RNAi or antisense nucleic acid molecule of  claim 4 . 
     
     
         14 . A method of detecting the CAT protein of  claim 1  in a sample, the method comprising contacting the sample with an isolated antibody that selectively binds to the CAT protein and determining whether the antibody binds to the CAT protein. 
     
     
         15 . A method of detecting the nucleic acid molecule of  claim 3  in a sample, the method comprising contacting the sample with an oligonucleotide that specifically hybridizes to the nucleic acid molecule and determining whether the oligonucleotide binds to the nucleic acid molecule. 
     
     
         16 . A method of diagnosing, prognosing, or determining risk of cancer in a subject, the method comprising detecting at least one molecule in a sample, wherein the presence or abundance of the molecule is indicative of cancer, and wherein the molecule is selected from the group consisting of:
 a) CAT proteins comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-4, 9, 11-12, 16-19, 24-36, 51-59, 69-74, 81-85, 91-102, 115-116, 119-121, 127-134, 144-145, 148-149, 152-159, 168-174, and 182-183;   b) antibodies that selectively bind to the CAT protein of a);   c) nucleic acid molecules comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:5-8, 10, 13-15, 20-23, 37-50, 60-68, 75-80, 86-90, 103-114, 117-118, 122-126, 135-143, 146-147, 150-151, 160-167, 175-181, 184-185 and nucleotide sequences that encode the CAT protein of a); and   d) nucleic acid molecules comprising a nucleotide sequence that is completely complementary to the nucleic acid molecule of c).   
     
     
         17 . A method of treating cancer, the method comprising administering a therapeutically effective amount of the antibody of  claim 5  to a subject. 
     
     
         18 . A method of screening agents, the method comprising contacting the CAT protein of  claim 1  or a cell that expresses the CAT protein with an agent, and assaying for whether the agent binds to the CAT protein or modulates the function, activity, or expression of the CAT protein. 
     
     
         19 . A composition comprising the agent identified by the method of  claim 18  and a pharmaceutically acceptable carrier. 
     
     
         20 . A method of determining or predicting the effectiveness of a treatment or selecting a treatment for administration to a subject having cancer, the method comprising detecting the presence, abundance, or activity of the CAT protein of  claim 1  in a sample and determining or predicting the effectiveness of the treatment or selecting the treatment for administration based on the presence, abundance, or activity of the CAT protein.