COMPOSITIONS AND METHODS FOR THE DIAGNOSIS AND TREATMENT OF TUMOR
The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.
1 . A method of diagnosing in a mammal the presence of a tumor in which a nucleic acid encoding a protein having sulfatase activity and comprising an amino acid sequence having at least 95% amino acid sequence identity to:
(a) the polypeptide of SEQ ID NO:9;
(b) the polypeptide of SEQ ID NO:9, lacking its associated signal peptide; or
(c) a polypeptide encoded by the nucleotide sequence of SEQ ID NO:4
is significantly overexpressed, the method comprising (i) determining the level of expression of the nucleic acid in a test sample of tissue cells obtained from the mammal and (ii) comparing the level of expression of (i) with the level of expression of the nucleic acid in a control sample, wherein a significantly higher level of expression of the nucleic acid encoding the protein in the test sample, as compared to the control sample, is indicative of the presence of a tumor in which the nucleic acid is significantly overexpressed, and wherein the tumor is selected from a bone, rectum, head and neck, kidney, ovarian, pancreatic, soft tissue, urinary tract, uterine, and brain tumor.
2 . The method of claim 1 , wherein determining the level of expression of the nucleic acid comprises employing an oligonucleotide in an in situ hybridization or RT-PCR analysis.
3 . The method of claim 1 , wherein determining the level of expression of the nucleic acid comprises employing an antibody in an immunohistochemistry or Western blot analysis.
4 . The method of claim 1 , wherein the protein comprises:
(a) the amino acid sequence of SEQ ID NO:9;
(b) the amino acid sequence of SEQ ID NO:9, lacking its associated signal peptide sequence; or
(c) an amino acid sequence encoded by the nucleotide sequence of SEQ ID NO:4.
5 . The method of claim 1 , wherein the test sample of tissue cells are tumor stromal cells.
6 . A method of binding an antibody to a tumor cell that expresses a protein having sulfatase activity and comprising an amino acid sequence having at least 95% amino acid sequence identity to:
(a) the amino acid sequence of SEQ ID NO:9;
(b) the amino acid sequence of SEQ ID NO:9, lacking its associated signal peptide; or
(c) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence of SEQ ID NO:4,
said method comprising contacting said tumor cell with an antibody that binds to said protein and allowing the binding of said antibody to said protein to occur, thereby binding said antibody to said tumor cell, wherein said tumor cell is selected from a bone, rectum, head and neck, kidney, ovarian, pancreatic, soft tissue, urinary tract, uterine, and brain tumor cell.
7 . The method of claim 6 , wherein said antibody is a monoclonal antibody.
8 . The method of claim 6 , wherein said antibody is an antibody fragment.
9 . The method of claim 6 , wherein said antibody is a chimeric or a humanized antibody.
10 . The method of claim 6 , wherein said antibody is conjugated to a growth inhibitory agent.
11 . The method of claim 6 , wherein said antibody is conjugated to a cytotoxic agent.
12 . The method of claim 6 , wherein said cytotoxic agent is selected from the group consisting of maytansinoid and calicheamicin.
13 . The method of claim 6 , wherein the tumor cell is a tumor stromal cell.