JP2002527758A - Methods for diagnosing, monitoring, staging, imaging and treating prostate cancer - Google Patents

Abstract

  (57) [Summary] The present invention provides novel methods for detecting, diagnosing, monitoring, staging, predicting, imaging and treating prostate cancer.

Description

DETAILED DESCRIPTION OF THE INVENTION

FIELD OF THE INVENTION The present invention relates, in part, to newly developed assays for detecting, diagnosing, monitoring, staging, predicting, imaging and treating cancer, especially prostate cancer.

BACKGROUND OF THE INVENTION Prostate cancer is the most common malignancy in adult men, except for skin cancer, in the United States and is an increasingly common health problem. In 1996,
It has been estimated that 41,400 deaths were attributed to the disease in the United States alone, indicating that prostate cancer is the most common cause of death after lung cancer in the same population. If diagnosed and treated early, the chances of cure are quite high when the cancer is still limited to the prostate.

[0003] Treatment decisions for an individual are related to the stage of prostate cancer present in the individual.
A common classification of the spread of prostate cancer is the American Urological Association (AUA)
Developed by The AUA system classifies prostate tumors into four stages, AD. Stage A is a microscopic cancer inside the prostate, and additionally stages A1 and A2
Is subdivided into Lower stage A1 is a well-differentiated cancer restricted to one site inside the prostate. Treatment is generally observation, radical prostatectomy, or radiation therapy. Lower stage A2 is a moderately to poorly differentiated cancer at many sites inside the prostate. Treatment is radical prostatectomy or radiation therapy. Stage B is a palpable mass inside the prostate and is further subdivided into lower stages B1 and B2. In lower stage B1, the cancer forms small nodules in one lobe of the prostate. Lower stage B2
In, the cancer forms large or multiple nodules or occurs in both lobes of the prostate. Treatment of lower stages B1 and B2 is radical prostatectomy or radiation therapy. Stage C is a large cancer mass that contains most or all of the prostate and is further subdivided into two sub-stages. In lower stage C1, the cancer forms a continuous mass that may extend outside the prostate. In lower stage C2, the cancer forms a continuous mass that infiltrates the surrounding tissue. The treatment of both lower stages is radiation therapy, with or without drugs to address this cancer. The fourth stage, stage D, is metastatic cancer and is subdivided into two sub-stages. In lower stage D1, cancer appears in the pelvic lymph nodes. In lower stage D2, the cancer involves tissues outside the lymph nodes. Both lower stages of treatment are systemic drugs to address cancer as well as pain.

[0004] However, current staging methods for prostate cancer are limited. As many as 50% of prostate cancers initially staged as A2, B or C are stage D and metastatic. Finding metastases is important because patients with metastatic cancer have a worse prognosis than patients with localized cancer and require treatment that is significantly different from patients with localized cancer It is. The 5-year survival rates for patients with localized and metastatic prostate cancer are 93% and 29%, respectively.

[0005] Thus, to staging cancer in humans to determine if such cancers have metastasized, and to monitor the course of non-metastatic cancer in humans with respect to the onset of metastasis There is a great need for more sensitive and accurate methods.

[0006] A number of proteins in the public domain have been found to be useful as diagnostic markers for prostate cancer. This diagnostic marker is referred to herein as a cancer-specific gene, or CSG, and includes, but is not limited to, Pro109, a human zinc-α2-glycoprotein (
Freje et al. Genomics 1993 18 (3): 575-587); Pro112 (Liebhaber et al. Nuc), a protein with a zinc finger motif and rich in human cysteine.
leic Acid Research 1990 18 (13): 3871-3879; WO9514772 and WO9845436); Pro111, a prostate-specific transglutaminase (Dubbink et al. Genomic)
s 1998 51 (3): 434-444); which has transmembrane, LDLR, and SRCR domains;
Pro115 (Paolon, a novel serine protease located at 1q22.3
i-Giacobino et al. Genomics 1997 44 (3): 309-320; WO9837418 and WO987093)
Pro110, a human breast cancer fatty acid synthase (US Pat. No. 5,665,874 and W
O9403599); Pro113 which is a homeobox gene, HOXB13 (Steini
cki et al. J. Invest. Dermatol. 1998 111: 57-63); human tetraspan NET
-1 which is Pro114 (WO9839446); and P which is a human JM27 protein
ro118 (WO9845435). These CSG ESTs have SEQ ID NO: 1.
, 3, 5, 7, 9, 11, 13 and 15, while the full length contigs of such CSGs are shown as SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14 and 16, respectively. Additional CSGs for use in the present invention are represented herein by SEQ ID NOs: 17, 18, 19 and 20.

[0007] The present invention provides methods for detecting, diagnosing, monitoring, staging, predicting, imaging, and treating prostate cancer with a cancer-specific gene referred to herein as CSG. For the purposes of the present invention, CSG comprises the polynucleotide sequence SEQ I
D NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 1
It specifically refers to a native protein expressed by a gene comprising 4, 15, 16, 17, 18, 19 or 20. Also, “CSG” means in this specification,
Due to the degeneracy in gene coding, SEQ ID NOs: 1-2
Polynucleotides that contain mutations in the nucleotide sequence as compared to 0, but still encode the same protein. In addition, the CSG used herein
Means the polynucleotide sequence SEQ ID NO: 1, 2, 3, 4
, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 1
Natural mRNA encoded by a gene comprising 8, 19 or 20, polynucleotide sequence SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9
, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20
Or under stringent conditions, SEQ ID NO:
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,
The level of polynucleotide that can hybridize to 16, 17, 18, 19 or 20 antisense sequences.

[0008] Other objects, features, advantages and aspects of the present invention will become apparent to those skilled in the art from the following description. However, it is to be understood that the following description and specific examples, while illustrating preferred embodiments of the present invention, are provided by way of illustration only. Various changes and modifications within the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following description and from reading the other parts of the present disclosure.

SUMMARY OF THE INVENTION To achieve the above and other goals, the object of the present invention is to provide a method for altering the level of CSG in a cell, tissue or body fluid, preferably of the same cell, tissue or body fluid type. Providing a method for diagnosing the presence of prostate cancer by analyzing the level of CSG in normal human controls, wherein the level of CSG in patients versus normal human controls is analyzed. The change is associated with prostate cancer.

[0010] Further provided is a method of diagnosing metastatic prostate cancer in a patient having prostate cancer not known to have metastasized, the method comprising the steps of diagnosing a human suspected of having metastatic prostate cancer. Identifying a patient; analyzing a cell, tissue, or fluid sample from such a patient for CSG; determining the level of CSG in such cells, tissue, or fluid, preferably in the same cell, tissue, or fluid. By comparing with the levels of CSG in normal human controls of the type, wherein the increase in CSG levels in patients versus normal human controls is associated with metastatic prostate cancer.

[0011] Also provided by the present invention is a method of staging such cancer in a human having prostate cancer, the method identifying a human patient having such cancer; A sample of cells, tissues, or fluids obtained from such a patient is analyzed for CSG; the level of CSG in such cells, tissues, or fluids is preferably determined by normal humans of the same cell, tissue or fluid type By comparing to the level of CSG in a control sample, where the increase in CSG levels in the patient versus normal human control is associated with ongoing cancer, the decrease in CSG levels is in decline or Associated with cancer in remission.

[0012] Further provided is a method of monitoring such cancer in a human having prostate cancer for the onset of metastasis. The method identifies human patients with such cancers that are not known to have metastasized; periodically analyzing samples of cells, tissues, or body fluids from such patients for CSG; Comparing the level of CSG in a healthy cell, tissue or body fluid with a level of CSG in a normal human control sample, preferably of the same cell, tissue or body fluid type, wherein the patient versus normal Increased CSG levels in human controls are associated with metastatic cancer.

[0013] Further provided is a method of monitoring the change in the stage of such cancer in a person with such cancer by examining the level of CSG in the person with prostate cancer. The method identifies a human patient having such a cancer;
Samples of cells, tissues, or body fluids obtained from such patients are periodically analyzed for CSG; CSG levels in such cells, tissues, or body fluids are preferably measured for the same cell, tissue, or body fluid type. Comprising comparing the level of CSG in a sample of a normal human control, wherein the increase in the level of CSG in the patient versus the normal human control is associated with ongoing cancer and the level of CSG is decreased. Is associated with declining or remissioning cancer.

[0014] Further provided is a method of designing a novel therapeutic agent targeting CSG for use in imaging and treating prostate cancer. For example, in one embodiment, a therapeutic agent such as an antibody targeting CSG or a fragment of such an antibody is
It can be used to detect or image the localization of CSG in a patient for the purpose of detecting or diagnosing a disease or condition. Such antibodies can be polyclonal, monoclonal, or omniclonal, or can be produced by molecular biology techniques. As used throughout this specification,
The term "antibody" is also intended to include aptamers and single-stranded oligonucleotides, such as those obtained from the in vitro evolution protocol well known to those skilled in the art, referred to as SELEX. Antibodies can be labeled with a variety of detectable labels, including, but not limited to, radioisotopes and paramagnetic metals. Therapeutic agents such as antibodies or fragments thereof may also be CSG
Can be used in the treatment of diseases characterized by the expression of In therapeutic applications,
The antibodies can be used with or without derivatization to cytotoxic agents such as radioisotopes, enzymes, toxins, drugs or prodrugs.

[0015] Other objects, features, advantages and aspects of the present invention will become apparent to those skilled in the art from the following description. However, it is to be understood that the following description and specific examples, while illustrating preferred embodiments of the present invention, are provided by way of illustration only. Various changes and modifications within the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following description and from reading the other parts of the present disclosure.

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the level of CSG in a human patient in a normal human control.
To both quantitative and qualitative diagnostic assays and methods for detecting, diagnosing, monitoring, staging and predicting cancer by comparison with those of For the purposes of the present invention, what CSG levels mean is, in particular, the polynucleotide sequence SEQ I
D NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 1
It is a natural protein expressed by a gene containing 4, 15, 16, 17, 18, 19 or 20. Also, "CSG" herein means that due to degeneracy in gene coding, it contains mutations in the nucleotide sequence as compared to SEQ ID NOs: 1-20, but still encodes the same protein Polynucleotide. The natural protein to be detected is
It may be a degradation product, a complex of molecules or chemically modified. In addition, as used herein, CSG means polynucleotide sequence SEQ ID
NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14
MRNA, polynucleotide sequence SEQ ID NO: 1,2,3, encoded by a gene comprising, 15, 16, 17, 18, 19, or 20
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,
SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 1 at the level of the gene containing 18, 19 or 20 or under stringent conditions.
The level of polynucleotide that can hybridize to 2, 13, 14, 15, 16, 17, 18, 19, or 20 antisense sequences. Such levels, including determination of normal and abnormal levels, are preferably determined in at least one cell, tissue and / or body fluid. Thus, for example, a normal control body fluid,
A diagnostic assay according to the present invention for diagnosing CSG protein overexpression as compared to a cell or tissue sample may be used to diagnose the presence of prostate cancer.

[0017] All methods of the invention may optionally include determining the level of CSG as well as other cancer markers. In addition to CSG, other cancer markers useful in the present invention depend on the cancer being tested and are well known to those skilled in the art. Diagnostic Assays The present invention relates to analyzing changes in the level of CSG in a cell, tissue or body fluid relative to the level of CSG in a cell, tissue or body fluid, preferably of the same type, obtained from a normal human control. Thereby provide a method for diagnosing the presence of prostate cancer, wherein increased levels of CSG in patients versus normal human controls are associated with the presence of prostate cancer.

Without limiting the invention, in general, in the case of a quantitative diagnostic assay, a positive result indicating that the patient to be tested has cancer has cells, tissues or cancer marker markers such as CSG. A fluid level, preferably the same cells of a normal human control,
At least 2 times higher, most preferably at least 5 times higher than in tissues or body fluids.

[0019] The invention also provides a method of diagnosing metastatic prostate cancer with respect to the onset of metastasis in a patient having prostate cancer that has not yet metastasized. In the method of the present invention, metastasis may have occurred (but metastasis is not known in advance).
A human cancer patient suspected of having prostate cancer is identified. This can be accomplished by various means known to those skilled in the art.

In the present invention, determining the presence of CSG levels in cells, tissues or body fluids is particularly useful for distinguishing between non-metastatic and metastatic prostate cancer. Existing techniques have difficulty distinguishing metastatic prostate cancer from non-metastatic prostate cancer, and the choice of appropriate treatment often depends on knowing such.

In the present invention, the cancer marker level measured in the above-mentioned cell, tissue or body fluid is CSG, which is preferably the level of CSG in a normal human control of the same cell, tissue or body fluid type. Compare with level. That is, if the cancer marker being observed is exactly CSG in serum, this level is preferably compared to the level of CSG in serum of a normal human control. Elevated CSG in patients versus normal human controls is associated with metastatic prostate cancer.

Without limiting the invention, generally, in the case of a quantitative diagnostic assay, a positive result indicating that the cancer has metastasized in the patient being tested or monitored includes:
The cell, tissue or fluid level of a cancer marker such as CSG is at least two times higher, and most preferably at least five times higher than in a normal patient, preferably in the same cells, tissues or fluids.

As used herein, a normal human control includes a human patient without cancer and / or a non-cancer sample obtained from the patient; in the method for diagnosing or monitoring for metastasis, A normal human control may also preferably include a sample obtained from a human patient that has been reliably determined to have prostate cancer that has not metastasized. Staging The invention also provides a method of staging prostate cancer in a human patient.
The method includes identifying a human patient with such a cancer and analyzing cells, tissues, or body fluids obtained from such a human patient for CSG. next,
The determined CSG level in the patient is compared to the level of CSG in a normal human control, preferably of the same cell, tissue or fluid type, wherein the increase in CSG levels in a human patient versus a normal human control Is associated with ongoing cancer and C
Decreased levels of SG (but still above true normal levels) are associated with declining or remissioning cancer. Monitoring Also provided is a method of monitoring such cancer in a human patient with prostate cancer for the onset of metastasis. This method identifies human patients with such cancers that are not known to have metastasized; periodically analyzes cells, tissues, or fluids from such human patients for CSG; Comparing the determined CSG level in the patient to the level of CSG in a normal human control, preferably of the same cell, tissue or fluid type, wherein the CSG in a human patient versus a normal human control Increased levels are associated with metastatic cancer. In this method, the normal human control sample may also include a previous patient sample.

[0024] Further provided by the present invention is a method of monitoring changes in the stage of such cancer in a human patient having prostate cancer. The method includes identifying a human patient with such a cancer; periodically analyzing cells, tissues, or fluids obtained from such a human patient for CSG; determining the determined CSG levels in the human patient. ,
Preferably, the method comprises comparing the level of CSG in a normal human control of the same cell, tissue or fluid type, wherein an increase in the level of CSG in a human patient versus a normal human control progresses through the stage. It is associated with cancers in the middle, and reduced levels of CSG are associated with cancers that are declining or in remission. In this method, the normal human control sample may also include a previous patient sample.

Patient monitoring for the onset of metastasis is regular, preferably performed quarterly. However, this frequency may vary depending on the cancer, the individual patient, and the stage of the cancer. Assay Techniques Assay techniques that can be used to determine levels of expression (including protein levels) of a gene such as CSG of the present invention in a sample obtained from a patient are well-known to those of skill in the art. Such assay methods include, but are not limited to, radioimmunoassay, reverse transcription PCR (RT-PCR) assay, immunohistochemical assay,
In situ hybridization, competitive binding assays, western blot analysis, ELISA and proteomic approaches: include two-dimensional gel electrophoresis (2D electrophoresis) and non-gel based techniques such as mass spectrometry or protein interaction profiling. Of these, ELISA is often preferred for diagnosing expressed proteins of genes in biological fluids.

An ELISA involves first making an antibody specific to CSG, preferably a monoclonal antibody, if not readily available from commercial sources. In addition, a reporter antibody that specifically binds to CSG is generally generated. The reporter antibody is attached to a detectable reagent such as a radioactive, fluorescent or enzymatic reagent, eg, horseradish peroxidase enzyme and alkaline phosphatase.

To perform the ELISA, an antibody specific for CSG is incubated on the surface of a solid support, such as a polystyrene dish, that binds the antibody. The non-specific proteins, such as bovine serum albumin, are then incubated to cover the free protein binding sites on the dish surface. The sample to be analyzed is then incubated in the dish, during which time CSG binds to the specific antibody attached to the polystyrene dish. Wash away unbound sample with buffer. A reporter antibody specifically directed to CSG and conjugated to a detectable reagent such as horseradish peroxidase is placed in a dish, resulting in binding of the reporter antibody to the monoclonal antibody conjugated to CSG.
Unattached reporter antibody is then washed away. Reagents for peroxidase activity, including a colorimetric substrate, are then added to the dish. Immobilized peroxidase bound to the CSG antibody produces a colored reaction product. The amount of color generated at a given time is proportional to the amount of CSG protein present in the sample. Quantitative results are generally obtained by reference to a standard curve.

[0028] A competition assay can also be used, in which an antibody specific for CSG is attached to a solid support, and labeled CSG and a sample obtained from a host are passed over the solid support. The amount of label attached to the solid support and detected was determined by the amount of CSG in the sample.
Can be correlated with the amount of

[0029] Nucleic acid methods can also be used to detect CSG mRNA as a marker for prostate cancer. Polymerase chain reaction (PCR), other nucleic acid methods such as ligase chain reaction (LCR) and nucleic acid sequence based amplification (NASABA)
Can be used to detect malignant cells for the purpose of diagnosing and monitoring various malignancies. For example, reverse transcription PCR (RT-PCR) is a powerful technique and can be used to detect the presence of a particular mRNA population in a complex mixture of thousands of other mRNA species. In RT-PCR, the mRNA species is first reverse transcribed using reverse transcriptase to complementary DNA (cDNA); the cDNA is then amplified as in a standard PCR reaction. RT-PCR, therefore, allows amplification of a single species of mRN
The existence of A can be clarified. Thus, if the mRNA is very specific for the cell that produces it, RT-PCR can be used to identify the presence of a particular type of cell.

[0030] Hybridization (ie, gridding) to clones or oligonucleotides arrayed on the surface of a solid support can be used to detect expression of the gene and to quantify the level of expression of the gene. In this technique, a cDNA encoding the CSG gene is immobilized on a substrate. The substrate may be of any suitable type, including glass, nitrocellulose, nylon or plastic,
It is not limited to these. At least a portion of the DNA encoding the CSG gene is attached to a substrate and then isolated from the tissue of interest.
Incubate with the analyte, which may be NA or a complementary DNA (cDNA) copy of this RNA. Hybridization between the DNA bound to the substrate and the analyte can be detected and quantified by a number of means, such as those designed to detect radioactive or fluorescent labeling or hybrids of the analyte. A second molecule includes, but is not limited to. Quantification of the level of gene expression can be performed by comparing the intensity of the signal obtained from the subject with that obtained from a known standard sample. To obtain a standard sample, the target gene is transcribed in vitro, the yield is quantified, and the material is then used to generate a standard curve.

[0031] Among the proteomic approaches, 2D electrophoresis is a technique well known to those skilled in the art. Separation of individual proteins from a sample, such as serum, is accomplished using sequential separation of proteins, usually on a polyacrylamide gel surface, with various properties. First, proteins are separated by size using current. Because the current acts uniformly on all proteins, smaller proteins travel farther on the gel surface than larger proteins. In the second dimension, a current is passed perpendicular to the first dimension, separating the proteins not by size, but by the specific charge that each protein carries. The result of a 2D separation is a square gel in which each protein occupies a unique spot, as no two proteins with different sequences will be identical in both size and charge. Analysis of spots using chemical or antibody probes, or subsequent protein microsequencing, can reveal the relative abundance of a given protein and the identity of the protein in a sample.

The above tests can be performed on samples obtained from various cells, body fluids and / or tissue extracts, such as homogenates or solubilized tissues obtained from patients. Tissue extracts are routinely obtained from tissue biopsies and dissected material. Body fluids useful in the present invention include blood, urine, saliva or any other bodily secretions or derivatives thereof. Blood is intended to include whole blood, plasma, serum or any derivative of blood. In vivo targeting of CSG The identification of CSG described above is also useful in the rational design of novel therapeutics for imaging and treating cancer, especially prostate cancer. For example, in one embodiment, an antibody that specifically binds to CSG can be raised and used in vivo in a patient suspected of having prostate cancer. Antibodies that specifically bind to CSG can be injected into patients suspected of having prostate cancer for diagnostic and / or therapeutic purposes. The production and use of antibodies for in vivo diagnosis is well known in the art. For example, antibody-chelators labeled with indium-111 have been described for use in radioimmunosyntographic imaging of tumors that express carcinoembryonic antigen (Sumerdon et al. Nucl. Med. Biol. 1990 17
: 247-254). In particular, such antibody-chelators have been used in the detection of tumors in patients suspected of having recurrent colorectal cancer (Griffin et al. J. Cl.
in. Onc. 1991 9: 631-640). Antibodies using paramagnetic ions as labels for use in magnetic resonance imaging have also been described (Lauffer, RB Magnetic R
esonance in Medicine 1991 22: 339-342). Antibodies directed against CSG can be used in a similar manner. A labeled antibody that specifically binds to CSG can be injected into a patient suspected of having prostate cancer for the purpose of diagnosing or staging the patient's disease state. The label used is chosen according to the imaging format used. For example, radioactive labels such as indium-111, technetium-99m or iodine-131 can be used for planar scanning or single photon tomography (SPECT). Positron emitting labels such as fluorine-19 can be used in positron emission tomography.
Paramagnetic ions such as gadolinium (III) or manganese (II) can be used in magnetic resonance imaging (MRI). Localization of the label allows measurement of the spread of the cancer. Also, the amount of label inside an organ or tissue makes it possible to determine whether cancer is present in this organ or tissue.

For patients diagnosed with prostate cancer, injection of an antibody that specifically binds to CSG may also have therapeutic benefit. Antibodies may be able to exert their therapeutic effects alone. Alternatively, the antibody can be conjugated to a cytotoxic agent such as a drug, toxin or radionuclide to enhance its therapeutic effect. Drug monoclonal antibodies have been described in the prior art, for example, in Garnett and Baldwin, Cancer Research 1986 46: 2407-.
2412. The use of toxins conjugated to monoclonal antibodies for the treatment of various cancers is also described in Pastan et al. Cell 1986 47: 641-648.
Yttrium-90 labeled monoclonal antibodies have been described for maximizing dose delivered to tumors and at the same time limiting toxicity to normal tissues (Goodwin an).
d Meares Cancer Supplement 1997 80: 2675-2680). Other cytotoxic radionuclides (
(Including, but not limited to, copper-67, iodine-131, and rhenium-186) can also be used for labeling antibodies to CSG.

[0034] Antibodies that can be used in such in vivo methods include polyclonal, monoclonal and omniclonal antibodies and antibodies produced by molecular biology techniques. Antibody fragments, as well as aptamers and single-stranded oligonucleotides, such as those obtained from in vitro evolution protocols well known to those skilled in the art, referred to as SELEX, can also be used.

Small molecules predicted by computer imaging to specifically bind to regions of the CSG can also be designed, synthesized, and tested for use in imaging and treating prostate cancer. In addition, the C identified herein
By assessing the ability of a molecule to bind to SG, a library of molecules can be screened for potential anti-cancer agents. Molecules identified in the library as being capable of binding CSG are prime candidates for further evaluation for use in treating prostate cancer.

EXAMPLES The present invention is further described by the following examples. This example is provided only to illustrate the invention by reference to specific examples. Such exemplifications illustrate particular embodiments of the invention, but are not intended to be limiting or limiting of the disclosed invention.

[0037] All of the examples outlined herein, unless otherwise specified, were performed using standard techniques well known and routine to those skilled in the art. Common molecular biology techniques in the following examples are described in Sambrook et al., MOLECULAR CLONING: A LABORATORY M
ANUAL, 2nd Ed .; Cold Spring Harbor Laboratory Press, Cold Spring Harbor,
It can be performed as described in standard laboratory manuals such as NY (1989). Example 1: Identification of CSG CSG was identified using Incyte using the Data Mining Cancer Leads Automatic Search Package (CLASP) developed by diaDexus LLC, Santa Clara, CA.
Performed by systematic analysis of data in the LIFESEQ database available from Pharmaceuticals, Palo Alto, CA.

CLASP performs the following steps: selection of highly expressed organ-specific genes based on abundance levels of the corresponding ESTs in the target organ versus all other organs; normal, tumor tissue, diseased tissue And analysis of the expression levels of each highly expressed organ-specific gene in a tumor or disease-related tissue library; selection of candidates demonstrating that the component EST was found only or more often in the tumor library. CLASP allows the identification of highly expressed organs and cancer-specific genes. The last manual in depth evaluation is then executed to complete the CSG selection.

The clones shown in Table 1 below are CSGs useful in diagnosing, monitoring, staging, imaging and treating prostate cancer.

[0040]

[Table 1]

Example 2: Relative quantification of gene expression Real-time quantitative PCR using a fluorescent Taqman probe was performed using Taq D
This is a quantitative detection system utilizing the 5'-3 'nuclease activity of NA polymerase.
This method uses an internal fluorescent oligonucleotide probe (Taqman) labeled with a 5 'reporter dye and a downstream 3' quencher dye. During PCR, the 5'-3 'nuclease activity of Taq DNA polymerase releases the reporter, and then the fluorescence of the reporter is measured using the model 7700 sequence detection system (PE applied
Biosystems, Foster City, CA, USA).

Using the amplification of the endogenous control, the amount of sample RNA added to the reaction is normalized and normalized for reverse transcriptase (RT) potency. Cyclophilin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ATPase, or 18S ribosomal RNA (rRNA) is used as this endogenous control. To calculate the relative quantification between all the samples examined, the target RNA level of one sample was used as a reference for the comparison results (calibrators). Quantitation based on the "Calibrator" is obtained using the standard curve method or the comparison method (user magazine # 2
: ABI PRISM 7700 sequence detection system).

[0043] Tissue distribution and target gene levels were evaluated for all samples in normal and cancerous tissues. Total RNA was extracted from normal and cancerous tissues, and from cancer and corresponding matched adjacent tissues. Subsequently, first-strand cDNA was prepared using reverse transcriptase, and a polymerase chain reaction was performed using primers specific to each target gene and a Taqman probe. The results were from ABI PRISM 7700
Analyzed using a sequence detector. Anonymous numbers are the relative levels of target gene expression in a particular tissue compared to calibrator tissue. Expression of clone ID 3424528H1 (Pro109): For CSG Pro109, real-time quantitative PCR was performed using the following primers. Forward primer: 5'-ATCAGAACAAAGAGGCTGTGTC-3 '(SEQ ID
NO: 21) Reverse primer: 5'-ATCTCTAAAGCCCCAACCTTC-3 '(SEQ ID N
O: 22) The anonymous numbers shown in Table 2 indicate the C called Pro109 in 12 normal different tissues.
Relative level of SG expression. All values are relative to a normal stomach (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0044]

[Table 2]

The relative levels of expression in Table 2 show that Pro109 mRNA expression
14.83) shows higher (11.24) in prostate compared to all other normal tissues analyzed. Pancreas (relative expression level 4.38)
It is the only other tissue that expresses significant mRNA for ro109.

The absolute numbers in Table 2 were obtained by analyzing a pool of specific tissue samples from different individuals. This cannot be compared to the anonymous numbers derived from RNA from a single individual's tissue sample in Table 3.

The absolute numbers shown in Table 3 are the relative levels of expression of Pro109 in 28 pairs of matching samples and 4 unmatched samples. All values are relative to a normal stomach (calibrator). A matched pair is formed by mRNA from a cancer sample of a particular tissue and mRNA from a normal adjacent sample of the same tissue from the same individual.

[0048]

[Table 3]

[0049]

[Table 4]

In analysis of matching samples, higher levels of expression were in the prostate, indicating a high degree of tissue specificity for prostate tissue. Among all samples analyzed different from the prostate, 4 cancer samples (13.5 for breast 1 and 16.1 for colon 1 of cancer samples)
1, liver 1 was 8.43 and lung 2 was 7.39) only mRN in prostate
It showed expression comparable to A expression. These results confirmed some tissue specificity obtained using a panel of normal pooled samples (Table 2).

In addition, levels of mRNA expression were compared in cancer samples and normal isogenic adjacent tissues from the same individual. This comparison indicates specificity for the cancer (eg, higher levels of mRNA expression in the cancer sample compared to the normal flanking region).
Table 3 shows the overexpression of Pro109 in six out of nine primary prostate cancer tissues compared to their respective normal neighbors. in this way,
66. Prostate matching samples tested (total of 9 prostate matching samples)
In 66%, overexpression in cancer tissue was observed.

Overall, in addition to the degree of tissue specificity, mRNA overexpression in 66.66% of the primary prostate matching samples tested makes Pro109 a diagnostic marker for prostate cancer. Indicates that Expression of clone ID 578349H1 (Pro112): For CSG Pro112, real-time quantitative PCR was performed using the following primers. Forward primer: 5'-TGCCGAAGAGGTTCAGGTGC-3 '(SEQ ID NO:
23) Reverse primer: 5'-GCCACAGGTGGTACTGTCCAGAT-3 '(SEQ ID
NO: 24) The anonymous numbers shown in Table 4 are for CSG Pro112 in 12 normal different tissues.
Is the relative level of expression. All values are relative to normal thymus (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0053]

[Table 5]

The relative levels of expression in Table 4 show that Pro112 mRNA expression was the third highest expressed in a pool of normal prostate tissue (after uterus and breast) compared to a total of 12 tissues analyzed. Indicates a gene. The anonymous numbers in Table 4 were obtained by analyzing a pool of specific tissue samples from different individuals. These results demonstrate that Pro112 mRNA expression is prostate-specific, and thus indicate that Pro112 is a diagnostic marker for prostate disease, especially cancer. Expression of Clone ID 1794013H1 (Pro111): For CSG Pro111, real-time quantitative PCR was performed using the following primers. Forward primer: 5'-GCTGCAAGTTCTCCACATTGA-3 '(SEQ ID N
O: 25) Reverse primer: 5′-CAGCCGCAGGTGAAACAC-3 ′ (SEQ ID NO: 2
6) The anonymous numbers shown in Table 5 indicate CSG Pro111 in 12 normal different tissues.
Is the relative level of expression. All values are relative to normal testis (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0055]

[Table 6]

The relative levels of expression in Table 5 show that Pro111 mRNA expression
With the exception of 5166.6), it shows extraordinarily high levels in the pool of normal prostate (1483.72) compared to all other tissues analyzed. These results show that Pro1
11 demonstrates that mRNA expression indicates specificity for prostate and muscle.

The anonymous numbers in Table 5 were obtained by analyzing a pool of specific tissue samples from different individuals. This cannot be compared to the absolute numbers from RNA from single individual tissue samples in Table 6.

The absolute numbers shown in Table 6 are the relative levels of expression of Pro111 in 48 pairs of matching samples and 18 unmatched samples. All values are relative to normal testis (calibrator). A matched pair is formed by mRNA from a cancer sample of a particular tissue and mRNA from a normal adjacent sample of the same tissue from the same individual.

[0059]

[Table 7]

[0060]

[Table 8]

[0061]

[Table 9]

[0062]

[Table 10]

In analysis of the matching samples, higher levels of expression were in the prostate, indicating a high degree of tissue specificity for the prostate. These results confirm the tissue specificity results obtained with the normal pooled samples (Table 5).

In addition, the level of mRNA expression was compared between the cancer sample and isogenic normal adjacent tissues obtained from the same individual. This comparison indicates specificity for the cancer (eg, higher levels of mRNA expression in the cancer sample compared to the normal flanking region).
In Table 6, the overexpression of Pro111 in 5 out of 16 primary prostate cancer samples compared to their respective normal neighbors (prostate samples 2, 5, 10, 1).
7 and 19) are shown. Similar expression levels indicate that three unmatched prostate cancers (prostate samples 13, 14, 15) and two prostatitis (prostate samples 20, 21)
, And six benign prostate hyperplasia samples (prostate samples 22-27). Thus, in 31.25% of the prostate matching samples tested (16 prostate matching samples in total), there is overexpression in cancerous tissue.

Overall, in addition to high levels of tissue specificity, overexpression of mRNA in 31.25% of the tested prostate matching samples indicates that Pro111 is a diagnostic marker for prostate cancer. Show. Expression of Clone ID 2189835H1 (Pro115): For CSG Pro115, real-time quantitative PCR was performed using the following primers. Forward primer: 5'-TGGCTTTTGAACTCAGGGTCA-3 '(SEQ ID NO:
: 27) Reverse primer: 5'-CGGATGCACCTCGTAGACAG-3 '(SEQ ID NO:
: 28) The anonymous numbers shown in Table 7 indicate that CSG Pro115 in 12 normal different tissues.
Is the relative level of expression. All values are relative to normal thymus (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0066]

[Table 11]

The relative levels of expression in Table 7 indicate that Pro115 mRNA expression is higher in the prostate (337.79) compared to all other normal tissues analyzed. Lung (relative expression level 112.99) and breast (29.446)
ro115 is another tissue that expresses moderate levels of mRNA. These results confirm that Pro115 mRNA expression is highly specific for prostate.

The anonymous numbers in Table 7 were obtained by analyzing a pool of specific tissue samples from different individuals. This cannot be compared to the anonymous numbers from RNA from single individual tissue samples in Table 8.

The anonymous numbers shown in Table 8 are the relative levels of expression of Pro115 in 17 pairs of matching samples and 21 unmatched samples. All values are relative to normal thymus (calibrator). A matched pair is formed by mRNA from a cancer sample of a particular tissue and mRNA from a normal adjacent sample of the same tissue from the same individual.

[0070]

[Table 12]

[0071]

[Table 13]

[0072] Higher levels of expression were found in the prostate, indicating a high degree of tissue specificity for prostate tissue. Among all samples analyzed different from the prostate, two cancer samples (116.97 for colon 2 and 261.4 for ovary 2) and five normal adjacent tissue samples (small intestine 2, colon 1, colon 2, kidney Only 1 and lung 2) showed expression comparable to mRNA expression in prostate. These results are shown in a panel of normal pooled samples (Table 7).
) Confirmed the tissue specificity results obtained.

In addition, the levels of mRNA expression were compared between cancer samples and isogenic normal adjacent tissues obtained from the same individual. This comparison indicates specificity for the cancer (eg, higher levels of mRNA expression in the cancer sample compared to the normal flanking region).
In Table 8, three of the four matched prostate cancer tissues (prostate samples 1, 5 and 8)
Higher expression of Pro115 in is shown.

Overall, in addition to the high level of tissue specificity, higher expression in 75% of the tested prostate matching samples indicates that Pro115 is a diagnostic marker for prostate cancer. Expression of Clone ID 3277219H1 (Pro110): For CSG Pro110, real-time quantitative PCR was performed using the following primers. Forward primer: 5'-CGGCAACCTGGGTAGTGAGTG-3 '(SEQ ID NO:
: 29) Reverse primer: 5'-CGCAGCTCCTTGTAAACTTCAG-3 '(SEQ ID
NO: 30) The anonymous numbers shown in Table 9 indicate CSG Pro110 in 12 normal different tissues.
Is the relative level of expression. All values are relative to normal small intestine (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0075]

[Table 14]

The relative levels of expression in Table 9 indicate that Pro110 mRNA expression is not as high in normal prostate (3.01) compared to all other normal tissues analyzed. .

The anonymous numbers in Table 9 were obtained by analyzing a pool of specific tissue samples from different individuals. This cannot be compared to the anonymous numbers derived from RNA from a single individual's tissue sample in Table 10.

The anonymous numbers shown in Table 10 are the relative levels of Pro110 expression in 33 pairs of matching samples. All values are relative to normal small intestine (calibrator). A matched pair is formed by mRNA from a cancer sample of a particular tissue and mRNA from a normal adjacent sample of the same tissue from the same individual.

[0079]

[Table 15]

[0080]

[Table 16]

In cancer samples and isogenic normal adjacent tissues from the same individual, mRN
The level of A expression was compared. This comparison indicates specificity for the cancer (eg, higher levels of mRNA expression in the cancer sample compared to the normal flanking region). Table 10 shows Pro110 overexpression in eight of nine primary prostate cancer tissues compared to their respective normal adjacent parts (except prostate 4).
Thus, there was overexpression in cancer tissue in 88.88% of the cancer prostate tissue compared to the prostate matching samples tested (9 prostate matching samples in total).

Although not tissue specific, Pro110 mRNA expression is up-regulated in prostate cancer tissue. Overexpression of mRNA in 88.88% of the primary prostate matching cancer samples tested indicates that Pro110 is a diagnostic marker for prostate cancer. Pro110 is also used in the small intestine, colon, liver,
It showed overexpression in several other cancers tested, including breast and lung (Table 10).
Please refer to). Thus, Pro110 may be a diagnostic marker for other types of cancer. Clone ID 1857415; Expression of Gene ID 346880 (Pro113): For CSG Pro113, real-time quantitative PCR was performed using the following primers. Forward primer: 5′-CGGGAACCTCACCAGCCTATG-3 ′ (SEQ ID NO:
: 31) Reverse primer: 5'-CAGGCAACAGGGAGCATCATGT-3 '(SEQ ID NO:
: 32) The anonymous numbers shown in Table 11 are for CSG Pro11 in 12 normal different tissues.
3 is the relative level of expression. All values are relative to normal thymus (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0083]

[Table 17]

The relative levels of expression in Table 11 indicate that Pro113 mRNA expression is higher (489.44) in the prostate compared to all other normal tissues analyzed. Testis (relative expression level 0.35), uterus (0.13), thymus (1.
0), kidney (0.01) and brain (0.03) have lower mRN of Pro113.
Included in other tissues that express A levels. These results confirm that Pro113 mRNA expression is highly specific for prostate.

The anonymous numbers in Table 11 were obtained by analyzing a pool of specific tissue samples from different individuals. This is the RNA from a single individual's tissue sample in Table 12.
Cannot be compared with the anonymous number derived from

The anonymous numbers shown in Table 12 are the relative levels of expression of Pro113 in 78 pairs of matching tissue samples and 25 unmatched tissue samples. All values are relative to normal thymus (calibrator). A matched pair is formed by mRNA from a cancer sample of a particular tissue and mRNA from a normal adjacent sample of the same tissue from the same individual. In cancers where it was not possible to obtain a normal adjacent sample from the same individual (eg, ovary), samples from different normal individuals were analyzed.

[0087]

[Table 18]

[0088]

[Table 19]

[0089]

[Table 20]

[0090]

[Table 21]

[0091]

[Table 22]

[0092] In analysis of the matching samples, higher levels of expression were in the prostate, indicating a high degree of tissue specificity for prostate tissue. In addition to higher expression levels in prostate cancer samples, Pro113 expression was found to be induced (if not expressed in normal adjacent tissues) in some other cancers or to some extent upregulated. However, the increase in relative expression and fold in prostate cancer samples is much greater than in other cancer tissues.

In addition, the level of mRNA expression was compared between the cancer sample and isogenic normal adjacent tissues obtained from the same individual. This comparison indicates specificity for the cancer (eg, higher levels of mRNA expression in the cancer sample compared to the normal flanking region).
In Table 12, overexpression of Pro113 in 13 out of 16 primary prostate cancer tissues compared to their respective normal adjacent parts (prostate samples 2, 3, 4, 5).
, 6, 7, 8, 9, 10, 11, 13, 14, 16). Thus, 81.25% of the tested prostate matching samples had overexpression in cancerous tissue. The median level of expression in prostate cancer tissue samples is 609, while the median value for all other cancers is only 7.93 except for colon 9 in one colon sample. Colon 9 expression was similar to that found in prostate cancer tissue.

Overall, in addition to high levels of tissue specificity, overexpression of mRNA in 81.25% of the primary prostate matching samples tested indicates that Pro113
Indicates a diagnostic marker for prostate cancer. Expression is also found to be higher in other cancerous tissues compared to their respective normal adjacent tissues (kidney, bladder, testis, skin, stomach, small intestine, colon, pancreas, lung, breast, endometrium Uterus and ovary), thus indicating that Pro113 is a pan-cancer marker. Expression of clone ID 181463H1 (Pro114): For CSG Pro114, real-time quantitative PCR was performed using the following primers. Forward primer: 5'-TGGGCATCTGGGTGTTCA-3 '(SEQ ID NO: 3
3) Reverse primer: 5'-CGGCTGCGATGAGGAAGTA-3 '(SEQ ID NO:
34) The anonymous numbers shown in Table 13 indicate CSG Pro11 in 12 normal different tissues.
4 is the relative level of expression. All values are relative to normal muscle (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0095]

[Table 23]

The relative levels of expression in Table 13 indicate that Pro114 mRNA expression is higher in the prostate (1951) compared to all other normal tissues analyzed. Lung (relative expression level 882.2), kidney (414.4), testis (367)
. 1), and the uterus (139.6) have higher levels of Pro114 mRNA
Is another tissue that expresses These results indicate that Pro114 mRNA expression
To determine that it is more specific to the prostate than the other tissues examined.

[0097] The high level of tissue specificity indicates that Pro114 is a diagnostic marker for prostate disease, especially cancer. Expression of clone IDzr65g11 (Pro118): For CSG Pro118, real-time quantitative PCR was performed using the following primers. Forward primer: 5′-GCCCCATCTCCTGCTTCTTTAGT-3 ′ (SEQ ID
NO: 35) Reverse primer: 5'-CGTGGAGATGGCTCTGATGTTA-3 '(SEQ ID N
O: 36) The anonymous numbers shown in Table 14 indicate CSG Pro11 in 12 normal different tissues.
8 is the relative level of expression. All values are relative to a normal kidney (calibrator). This RNA sample is a commercially available pool and is derived from a pool sample of a particular tissue obtained from a different individual.

[0098]

[Table 24]

The relative levels of expression in Table 14 show that Pro118 mRNA expression is the third highest in prostate (962.1), following the endometrium (19282) and uterus (1064), which are female-specific tissues. Indicates that Testis (relative expression level 3
43.7) is the only other male tissue that expresses moderate levels of Pro118 mRNA. These results confirm that Pro118 mRNA expression is highly specific for reproductive tissues, including the prostate.

The abundances in Table 14 were obtained by analyzing a pool of specific tissue samples from different individuals. This is the RNA from a single individual's tissue sample in Table 15.
Cannot be compared with the anonymous number derived from

The absolute numbers shown in Table 15 are the relative levels of expression of Pro118 in 59 pairs of matching samples and 21 unmatched samples. All values are relative to a normal kidney (calibrator). Matched pairs are mRNA from a cancer sample of a particular tissue and mRNA from a normal adjacent sample of the same tissue from the same individual.
Formed by

[0102]

[Table 25]

[0103]

[Table 26]

[0104]

[Table 27]

[0105]

[Table 28]

[0106]

[Table 29]

In the analysis of matching samples, higher levels of expression were detected in prostate, endometrium,
It was found in testis and ovaries and showed a high degree of tissue specificity for reproductive tissues. These results confirmed the tissue specificity results obtained with a panel of normal pooled samples (Table 14).

In addition, the level of mRNA expression was compared between cancer samples and isogenic normal adjacent tissues from the same individual. This comparison indicates specificity for the cancer (eg, higher levels of mRNA expression in the cancer sample compared to the normal flanking region).
In Table 15, the overexpression of Pro118 in 5 of 14 primary prostate cancer tissues is compared to its respective normal adjacent part (prostate samples 1, 8, 10,
11, 15) are shown. Thus, 35.71% of the prostate matching samples tested (a total of 14 prostate matching samples) had overexpression in cancerous tissue. Pro118 expression was detected in three unmatched cancer tissues (prostate sample 9
, 13, 14) were also higher in two prostatitis (prostate samples 20, 21) and six benign hyperplastic tissues (prostate samples 22-27).

Overall, in addition to high levels of tissue specificity, overexpression of mRNA in 35.71% of the primary prostate matching samples tested indicates that Pro118
Indicates a diagnostic marker for prostate cancer.

[Sequence list]

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 35/00 C07K 16/32 C07K 16/32 C12Q 1/68 A C12N 15/09 ZNA G01N 33/577 B C12Q 1/68 A61K 49/02 A G01N 33/577 C12N 15/00 ZNAA (72) Inventor Kafarky, Robert 95134, California, United States of America, San Jose, Elan Village Lane 350, Apartment Number 218 F-term (reference) 4B024 AA01 AA12 BA45 CA01 HA15 4B063 QA19 QQ02 QQ03 QQ53 QQ79 QQ96 QR32 QR48 QR56 QS33 QS34 QX01 QX02 4C085 AA13 AA25 AA26 BB01 CC32 EE01 HH03 HH07 KA03 KA28 KA29 KA18 KA18

Claims (12)

[Claims] 1. A method for diagnosing the presence of prostate cancer in a patient, comprising: (a) determining the level of CSG in cells, tissues or body fluids in the patient; and (b) determining the CSG. Comparing the level to the level of CSG in cells, tissues or body fluids obtained from a normal human control, wherein the change in the determined level of CSG in said patient versus said normal human control is , Methods that are associated with the presence of prostate cancer. 2. A method of diagnosing prostate cancer metastasis in a patient, comprising: (a) identifying a patient with prostate cancer that is not known to have metastasized;
(B) determining the CSG level in a cell, tissue or fluid sample obtained from the patient; and (c) determining the determined CSG level of the CSG in a normal human control cell, tissue or fluid. Comparing the CSG level in said patient versus said normal human control.
The method wherein the increased level is associated with a metastatic cancer. 3. A method for staging prostate cancer in a patient with prostate cancer, comprising: (a) identifying a patient with prostate cancer; and (b) cells, tissue or fluid obtained from said patient. Determining the level of CSG in the sample of (c); comparing the determined level of CSG with the level of CSG in normal human control cells, tissues or body fluids. Established CSG in the patient versus the normal human control
The method wherein the increased level is associated with an ongoing cancer and the determined decrease in CSG levels is associated with a declining or remissioning cancer. 4. A method of monitoring prostate cancer in a patient for the onset of metastasis, comprising: (a) identifying a patient with prostate cancer not known to have metastasized;
(B) periodically determining the level of CSG in a cell, tissue, or body fluid sample obtained from said patient; and (c) determining said periodically determined CSG level in normal human control cells. Comparing the level of CSG in a tissue or body fluid with said one of said regularly increased CSG levels in said patient versus said normal human control. Related, method. 5. A method for monitoring a prostate cancer stage change in a patient, the method comprising: (a) identifying a patient with prostate cancer; and (b) cells, tissue, or fluid obtained from the patient. (C) comparing said periodically determined CSG level to the level of CSG in normal human control cells, tissues or body fluids; The method of any of the preceding claims, wherein any one increase in the regularly determined CSG level in the patient versus the normal human control is associated with an advanced stage cancer;
The method wherein the reduction is associated with a cancer whose stage is decreasing or in remission. 6. A method for identifying a potential therapeutic agent for use in imaging and treating prostate cancer, comprising screening the molecule for its ability to bind to CSG, wherein the molecule comprises CSG. The method wherein the ability to bind to is indicative that the molecule is useful in imaging and treating prostate cancer. 7. The CSG comprises SEQ ID NO: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 1,
7. The method of claim 1, 2, 3, 4, 5, or 6, comprising 9 or 20, or a polypeptide encoded thereby. 8. An antibody that specifically binds to CSG. 9. A method of imaging prostate cancer in a patient, comprising administering the antibody of claim 8 to said patient. 10. The method of claim 9, wherein said antibody is labeled with a paramagnetic ion or a radioisotope. 11. A method for treating prostate cancer in a patient, comprising the steps of:
A method comprising administering to the patient the antibody of claim 1. 12. The method of claim 11, wherein said antibody is conjugated to a cytotoxic agent.