Novel therapeutic targets in cancer

Abstract

The present invention relates to novel sequences for use in detection, diagnosis and treatment of cancers, especially lymphomas. The invention provides cancer associated (CA) polynucleotide sequences whose expression is associated with cancer. The present invention provides CA polypeptides associated with cancer that are present on the cell surface and present novel therapeutic targets against cancer. The present invention further provides diagnostic compositions and methods for the detection of cancer. The present invention provides monoclonal and polyclonal antibodies specific for the CA polypeptides. The present invention also provides diagnostic tools and therapeutic compositions and methods for screening, prevention and treatment of cancer.

1 - 67 . (canceled) 
     
     
         68 . A method of diagnosing cancer in a patient comprising detecting the presence of differential expression of a gene in a patient sample, said gene comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170, wherein the presence of differential expression of the gene in said sample is indicative of a patient who has cancer. 
     
     
         69 . The method of  claim 68  wherein the level of gene expression is determined by measuring mRNA levels, said mRNA having a sequence selected from the group consisting of SEQ ID NO: 5, 11, 13, 19, 27, 29, 35, 37, 39, 45, 51, 53, 55, 61, 63, 65, 67, 69, 71, 73, 75, 83, 89,91,93,95,97,99, 101, 103, 105, 107, 113, 115, 117, 123, 129, 137, 139, 141, 143, 145, 147, 149, 155, 157, 159, 161, 163, 165, 171, and 173, or the complement thereof. 
     
     
         70 . The method of  claim 68  wherein the differential expression is upregulation of expression of the gene as compared to a control. 
     
     
         71 . A method of screening for anti-cancer activity comprising:
 (a) contacting a cell that expresses a gene with a candidate anti-cancer agent, said gene comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170; and   (b) detecting a difference between the level of gene expression in the cell in the presence and in the absence of the candidate anti-cancer agent, wherein a difference between the level of gene expression in the cell in the presence and in the absence of the candidate anti-cancer agent indicates that the candidate anti-cancer agent has anti-cancer activity.   
     
     
         72 . The method of  claim 71  wherein the candidate anti-cancer agent is an antibody, small organic compound, small inorganic compound, or polynucleotide. 
     
     
         73 . The method of  claim 71  wherein the candidate anti-cancer agent is a monoclonal antibody. 
     
     
         74 . The method of  claim 72  wherein the antibody is a human antibody or humanized antibody. 
     
     
         75 . The method of  claim 71  wherein the polynucleotide is an antisense oligonucleotide or an siRNA. 
     
     
         76 . A method of screening drug candidates comprising:
 a) providing a cell that expresses a gene comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170, or fragment thereof;   b) adding a drug candidate to said cell; and c) determining the effect of said drug candidate on the expression of said gene.   
     
     
         77 . The method of  claim 76  wherein said gene encodes an mRNA having a sequence selected from the group consisting of SEQ ID NO: 5, 11, 13, 19, 27, 29, 35, 37, 39, 45, 51, 53, 55, 61, 63, 65, 67, 69, 71, 73, 75, 83, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 113, 115, 117, 123, 129, 137, 139, 141, 143, 145, 147, 149, 155, 157, 159, 161, 163, 165, 171, and 173, or the complement thereof. 
     
     
         78 . The method of  claim 76  wherein said determining comprises comparing the level of expression of the gene in the absence of said drug candidate to the level of expression in the presence of said drug candidate. 
     
     
         79 . A method of screening for a bioactive agent capable of binding to a protein, wherein said protein is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170, said method comprising:
 a) combining said protein and a candidate bioactive agent; and   b) determining the binding of said candidate agent to said protein.   
     
     
         80 . A method for screening for a bioactive agent capable of modulating the activity of a protein, wherein said protein is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170, said method comprising:
 a) combining said protein and a candidate bioactive agent; and   b) determining the effect of said candidate agent on the bioactivity of said protein.   
     
     
         81 . The method of  claim 80  wherein the protein has a sequence selected from the group consisting of SEQ ID NO: 6, 12, 14, 20, 28, 30, 36, 38, 40, 46, 52, 54, 56, 62, 64, 66, 68, 70, 72, 74, 76, 84, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 114, 116, 118, 124, 130, 138, 140, 142, 144, 146, 148, 150, 156, 158, 160, 162, 164, 166, 172, and 174. 
     
     
         82 . A method of evaluating the effect of a candidate cancer drug comprising:
 a) administering the drug to a patient;   b) removing a cell sample from said patient; and   c) determining alterations in the expression or activation of a gene in the cell sample comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170.   
     
     
         83 . The method of  claim 82  wherein gene expression is determined by measuring mRNA levels of said one or more genes, said mRNA having a sequence selected from the group consisting of SEQ ID NO: 5, 11, 13, 19, 27, 29, 35, 37, 39, 45, 51, 53, 55, 61, 63, 65, 67, 69, 71, 73, 75, 83, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 113, 115, 117, 123, 129, 137, 139, 141, 143, 145, 147, 149, 155, 157, 159, 161, 163, 165, 171, and 173, or the complement thereof. 
     
     
         84 . A method of diagnosing cancer comprising: a) determining the expression of one or more genes comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170, in a first tissue type of a first individual; and b) comparing the gene expression in a) to expression of the gene in a control, wherein a difference between the expression of the gene in the first tissue type of the first individual compared to expression of the gene in the control indicates that the first individual has cancer. 
     
     
         85 . The method of  claim 84  wherein the control is a known normal sample. 
     
     
         86 . A method for inhibiting the activity of a protein, wherein said protein is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 5, 11, 13, 19, 27, 29, 35, 37, 39, 45, 51, 53, 55, 61, 63, 65, 67, 69, 71, 73, 75, 83, 89, 91, 93,95,97,99, 101, 103, 105, 107, 113, 115, 117, 123, 129, 137, 139, 141, 143, 145, 147, 149, 155, 157, 159, 161, 163, 165, 171, and 173, said method comprising binding an inhibitor to said protein. 
     
     
         87 . The method of  claim 86  wherein the protein has a sequence selected from the group consisting of SEQ ID NO: 6, 12, 14, 20, 28, 30, 36, 38, 40, 46, 52, 54, 56, 62, 64, 66, 68, 70, 72, 74, 76, 84, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 114, 116, 118, 124, 130, 138, 140, 142, 144, 146, 148, 150, 156, 158, 160, 162, 164, 166, 172, and 174. 
     
     
         88 . A method of treating cancer comprising administering to a patient an inhibitor of a protein, wherein said protein is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170. 
     
     
         89 . The method of  claim 88  wherein the protein has a sequence selected from the group consisting of SEQ ID NO: 6, 12, 14, 20, 28, 30, 36, 38, 40, 46, 52, 54, 56, 62, 64, 66, 68, 70, 72, 74, 76, 84, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 114, 116, 118, 124, 130, 138, 140, 142, 144, 146, 148, 150, 156, 158, 160, 162, 164, 166, 172, and 174. 
     
     
         90 . A method of neutralizing the effect of a protein, wherein said protein is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 4, 10, 18, 26, 34, 44, 50, 60, 82, 88, 112, 122, 128, 136, 154, and 170, the method comprising contacting an agent specific for said protein with said protein in an amount sufficient to effect neutralization. 
     
     
         91 . The method of  claim 90  wherein the protein has a sequence selected from the group consisting of SEQ ID NO: 6, 12, 14, 20, 28, 30, 36, 38, 40, 46, 52, 54, 56, 62, 64, 66, 68, 70, 72, 74, 76, 84, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 114, 116, 118, 124, 130, 138, 140, 142, 144, 146, 148, 150, 156, 158, 160, 162, 164, 166, 172, and 174. 
     
     
         92 . An isolated antibody which specifically binds to a polypeptide having a sequence selected from the group consisting of a sequence selected from the group consisting of SEQ ID NO: 6, 12, 14, 20, 28, 30, 36, 38, 40, 46, 52, 54, 56, 62, 64, 66, 68, 70, 72, 74, 76, 84, 90, 92, 94, 96,98,100,102,104,106,108,114,116,118,124,130,138,140,142,144,146,148,150,156, 158, 160, 162, 164, 166, 172, and 174. 
     
     
         93 . The isolated antibody of  claim 92  wherein the antibody is a monoclonal antibody 
     
     
         94 . The isolated antibody of  claim 92  wherein the antibody is a human or humanized antibody.