Novel therapeutic targets in cancer
OwnerDavid W. Morris, Marc S. Malandroinventors
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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.
Claims73
An isolated nucleic acid comprising at least 10 contiguous nucleotides of a sequence selected from the group consisting of the polynucleotide sequences of SEQ ID NOS:
- 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 169, 171, 173, 175, 177, 179, 181, 183, and 185 shown in Tables 1-28, or its complement.
A microarray for detecting a cancer associated (CA) nucleic acid comprising:
- at least one probe comprising at least 10 contiguous nucleotides of a sequence selected from the group consisting of the polynucleotide sequences SEQ ID NOS:
- 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 169, 171, 173, 175, 177, 179, 181, 183, and 185 shown in Tables 1-28, or its complement.
An isolated polypeptide, encoded within an open reading frame of a CA sequence selected from the group consisting of the polynucleotide sequences of SEQ ID NOS:
- 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, 148, 154, 160, and 166 shown in Tables 1-28, or its complement.
A kit for diagnosing the presence of cancer in a test sample, said kit comprising at least one polynucleotide that selectively hybridizes to a CA polynucleotide sequence selected from the group consisting of the polynucleotide sequences SEQ ID NOS:
- 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, 148, 154, 160, and 166 shown in Tables 1-28, or its complement.
A kit for diagnosing the presence of cancer in a test sample, said kit comprising at least one polynucleotide that selectively hybridizes to the sequence of a polynucleotide sequence selected from the group consisting of the polynucleotide sequences SEQ ID NOS:
- 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 169, 171, 173, 175, 177, 179, 181, 183, and 185 shown in Tables 1-28, a fragment thereof, or their complement.
An electronic library comprising a polynucleotide, or fragment thereof, comprising a CA polynucleotide sequence selected from the group consisting of the polynucleotide sequences of SEQ ID NOS:
- 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, 148, 154, 160, and 166 shown in Tables 1-28, or its complement.
An electronic library comprising a polynucleotide, or fragment thereof, comprising a CA polynucleotide sequence selected from the group consisting of the polynucleotide sequences of SEQ D NOS:
- 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 169, 171, 173, 175, 177, 179, 181, 183, and 185 shown in Tables 1-28.
An electronic library comprising a polypeptide, or fragment thereof, comprising a CA polypeptide sequence selected from the group consisting of the polypeptide sequences of SEQ ID NOS:
- 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 170, 172, 174, 176, 178, 180, 182, 184, and 186 shown in Tables 1-28.
A method of screening for anticancer activity comprising:
- (a) providing a cell that expresses a cancer associated (CA) gene encoded by a nucleic acid sequence selected from the group consisting of the sequences SEQ ID NOS:
- 4, 10, 16, 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, 148, 154, 160, and 166 shown in Tables 1-28, or fragment thereof;
- (b) contacting a tissue sample derived from a cancer cell with an anticancer drug candidate;
- and
- (c) monitoring an effect of the anticancer drug candidate on an expression of the CA polynucleotide in the tissue sample.
A method for detecting cancer associated with expression of a polypeptide in a test cell sample, comprising the steps of:
- (i) detecting a level of expression of at least one polypeptide selected from the group consisting of SEQ ID NOS:
- 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 170, 172, 174, 176, 178, 180, 182, 184, and 186 shown in Tables 1-28, or a fragment thereof;
- and
- (ii) comparing the level of expression of the polypeptide in the test sample with a level of expression of polypeptide in a normal cell sample, wherein an altered level of expression of the polypeptide in the test cell sample relative to the level of polypeptide expression in the normal cell sample is indicative of the presence of cancer in the test cell sample.
A method for detecting cancer associated with expression of a polypeptide in a test cell sample, comprising the steps of:
- (i) detecting a level of activity of at least one polypeptide selected from the group consisting of SEQ ID NOS:
- 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 170, 172, 174, 176, 178, 180, 182, 184, and 186 shown in Tables 1-28, or a fragment thereof, wherein said activity corresponds to at least one activity for the polypeptide listed in Table 29;
- and
- (ii) comparing the level of activity of the polypeptide in the test sample with a level of activity of polypeptide in a normal cell sample, wherein an altered level of activity of the polypeptide in the test cell sample relative to the level of polypeptide activity in the normal cell sample is indicative of the presence of cancer in the test cell sample.
A method for detecting cancer associated with the presence of an antibody in a test serum sample, comprising the steps of:
- (i) detecting a level of an antibody against an antigenic polypeptide selected from the group consisting of SEQ ID NOS:
- 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, 144, 150, 156, 162, 168, 170, 172, 174, 176, 178, 180, 182, 184, and 186 shown in Tables 1-28, or antigenic fragment thereof;
- and
- (ii) comparing said level of said antibody in the test sample with a level of said antibody in the control sample, wherein an altered level of antibody in said test sample relative to the level of antibody in the control sample is indicative of the presence of cancer in the test serum sample.
A method for screening for a bioactive agent capable of modulating the activity of a CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the polynucleotide sequences SEQ ID NOS:
- 5, 11, 17, 23, 29, 35, 41, 47, 53, 59, 65, 71, 77, 83, 89, 95, 101, 107, 113, 119, 125, 131, 137, 143, 149, 155, 161, 167, 169, 171, 173, 175, 177, 179, 181, 183, and 185 shown in Tables 1-28, said method comprising:
- a) combining said CAP and a candidate bioactive agent;
- and
- b) determining the effect of the candidate agent on the bioactivity of said CAP.
A method for diagnosing cancer comprising:
- a) determining the expression of one or more genes comprising a nucleic acid sequence selected from the group consisting of the human genomic and mRNA sequences outlined in Tables 1-28, in a first tissue type of a first individual;
- and
- b) comparing said expression of said gene(s) from a second normal tissue type from said first individual or a second unaffected individual;
- wherein a difference in said expression indicates that the first individual has cancer.
A method for treating cancers comprising administering to a patient an inhibitor of a CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the human nucleic acid sequences in Tables 1-28.
Dependencies are inferred from the claim text.