NZ546842A

NZ546842A - Diagnosis and treatment of tumors

Info

Publication number: NZ546842A
Application number: NZ546842A
Authority: NZ
Inventors: Austin L Gurney; Mickey P Williams
Original assignee: Genentech Inc
Priority date: 2001-12-19
Filing date: 2002-10-16
Publication date: 2008-08-29

Abstract

A method for the diagnosis and treatment of a tumour in an isolated or a non-human mammal cell that expresses a specific Tumour-associated Antigenic Target (TAT) polypeptide of SEQ ID NO: 6. The use of such a method is also disclosed.

Description

<div class="application article clearfix" id="description"> c~l— NEW ZEALAND PATENTS ACT, 1953 No: Divided, out of No. 533736 Date: Dated 16 October 2002 COMPLETE SPECIFICATION DIAGNOSIS AND TREATMENT OF CANCER AND TUMORS We, GENETECH, INC., of 1 DNA Way, South San Francisco, California 94080-4990, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: DIAGNOSIS AND TREATMENT OF CANCER AND TUMORS FIKLD OF THE INVENTION The present invention is directed to the diagnosis and treatment of tumors in mammals BACKGROUND OF THE INVENTION • 10 15 20 25 Malignant tumors (cancers) are the second leading cause of death in the United States, after heart disease (Boring et al., CA Cancel J. Clin. 43:7 (1993)). Cancer is characterized by the increase in the number of abnormal, or neoplastic, cells derived from a normal tissue which proliferate to form a tumor mass, the invasion of adjacent tissues by these neoplastic tumor cells, and the generation of malignant cells which eventually spread via the blood or lymphatic system to regional lymph nodes and to distant sites via a process called metastasis. In a cancerous state, a cell proliferates under conditions in which normal cells would not grow. Cancer manifests itself in a wide variety of forms, characterized by different degrees of invasiveness and aggressiveness. In attempts to discover effective cellular targets for cancer diagnosis Mid therapy, researchers have sought to identify transmembrane or otherwise membrane-associated polypeptides that are specifically expressed on the surface of one or more particular type(s) of cancer cell as compared to on one or more normal non-cancerous cell(s). Often, such membrane-associated polypeptides are more abundantly expressed on the surface of the cancer cells as compared to on the surface of the non-cancerous cells. The identification of such tumor-associated cell surface antigen polypeptides has given rise to the ability to specifically target cancer cells for destruction via antibody-based therapies. In this regard, it is noted that antibody-based therapy has proved very effective in the treatment of certain cancans. For example, HERCEPUN® and RITUXAN® (both from Genentech Inc., South San Francisco, California) are antibodies that have been used successfully to treat breast cancer and non-Hodgkin's lymphoma, respectively. More specifically, HERCEPTIN® is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the extracellular domain of the human epidermal growth factor receptor 2 (HER2) proto-oncogene. HER2 protein overexpression is observed in 25-30% of primary breast cancers. RITUXAN® is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Both these antibodies are recombinantly produced in CHO cells. In other attempts to discover effective cellular targets for cancer diagnosis and therapy, researchers have sought to identify (1) non-membrane-associated polypeptides that are specifically produced by one or more particular type(s) of cancer cell(s) as compared to by one or more particular type(s) of non-cancerous normal cell(s), (2) polypeptides that are produced by cancer cells at an expression level that is significantly higher than that of one or more normal non-cancerous cell(s), or (3) polypeptides whose expression is specifically limited to only a single (or very limited number of different) tissue type(s) in both the cancerous and non-cancerous state la INTELLECTUAL PROPERTY OFFICE OF N.2. 1,6 APR 2008 (e.g., normal prostate and prostate tumor tissue). Such polypeptides may remain intracellularly located or may be secreted by the cancer cell. Moreover, such polypeptides may be expressed not by the cancer cell itself, but rather by cells which produce and/or secrete polypeptides having a potentiating or growth-enhancing effect on cancer cells. Such secreted polypeptides are often proteins that provide cancer cells with a growth advantage over normal cells and include such things as, for example, angiogenic factors, cellular adhesion factors, growth factors, and the like. Identification of antagonists of such non-membrane associated polypeptides would be expected to serve as effective therapeutic agents for the treatment of such cancers. Furthermore, identification of the expression pattern of such polypeptides would be useful for the diagnosis of particular cancers in mammals. Despite the above identified advances in mammalian cancer therapy, there is a great need for additional diagnostic and therapeutic agents capable of detecting the presence of tumor in a mammal and for effectively inhibiting neoplastic cell growth, respectively. Accordingly, it is an objective of the present invention to provide a method of diagnosing cancers and tumors and the means to treat same, or to at least provide the public with a useful choice. SUMMARY OF THE INVENTION In the present specification, Applicants describe for the first time the identification of various cellular polypeptides (and their encoding nucleic acids or fragments thereof) which are expressed to a greater degree on the surface of or by one or more types of cancer cell(s) as compared to on the surface of or by one or more types of normal non-cancer cells. Alternatively, such polypeptides are expressed by cells which produce and/or secrete polypeptides having a potentiating or growth-enhancing effect on cancer cells. Again alternatively, such polypeptides may not be overexpressed by tumor cells as compared to normal cells of the same tissue type, but rather may be specifically expressed by both tumor cells and normal cells of only a single or very limited number of tissue types (preferably tissues which are not essential for life, e.g., prostate, etc.). All of the above polypeptides are herein referred to as Tumor-associated Antigenic Target polypeptides ("TAT" polypeptides) and are expected to serve as effective targets for cancer therapy and diagnosis in mammals. In one aspect the present invention provides a method of inhibiting the growth of an isolated or non-human cancer cell that expresses a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), said method comprising contacting said cell with an antibody, TAT binding oligopeptide or TAT binding organic molecule that binds to said protein, the binding of said antibody, oligopeptide or organic molecule to said protein thereby causing an inhibition of growth of said cell. In another aspect the present invention provides a method of determining the presence of a protein in a sample suspected of containing said protein, wherein said protein has at least 80% amino acid sequence identity to : (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3, said method comprising exposing said sample to an antibody, TAT binding oligopeptide or TAT binding organic molecule that binds to said protein and determining binding of said antibody, oligopeptide or organic molecule to said protein in said sample, wherein binding of the antibody, oligopeptide or organic molecule to said protein is indicative of the presence of said protein in said sample. In another aspect the present invention provides a method of diagnosing the presence of a tumor in a mammal, said method comprising determining the level of expression of a gene encoding a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in any one of Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (followed by page 3 a) I OFFICE OF N Z 11, SEP 2007 Described is the use of an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for treatment or prevention of a cell proliferative disorder In another aspect the present invention provides use of a host cell comprising an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. In another aspect the present invention provides use of a host cell comprising an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for treating a tumor. Described is the use of a host cell comprising an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. In another aspect the present invention provides use of a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. In another aspect the present invention provides use of a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the fall-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for treating a tumor. 3b (followed by page 3 c) INTELLECTUAL PROPERTY OFFICE OF N.Z. 1SEP 2007 PCflFIVED In another aspect the present invention provides use of a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. In another aspect the present invention provides use of an antibody, oligopeptide or TAT binding organic molecule that binds a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. In another aspect the present invention provides use of an antibody, oligopeptide or TAT binding organic molecule that binds a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for treating a tumor. Described is the use of an antibody, oligopeptide or TAT binding molecule that binds a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (followed by page 3d) 3c (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. Described but not claimed is an isolated nucleic acid molecule having a nucleotide sequence that encodes a tumor-associated antigenic target 395 polypeptide or fragment thereof (a "TAT" 395 polypeptide). Described is an isolated nucleic acid molecule comprising a nucleotide sequence having at least about 80% nucleic acid sequence identity, alternatively at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity, to (a) a DNA molecule encoding a full-length TAT polypeptide having an amino acid sequence as disclosed herein, a TAT polypeptide amino acid sequence lacking the signal peptide as disclosed herein, an extracellular domain of a transmembrane TAT polypeptide, with or without the signal peptide, as disclosed herein or any other specifically defined fragment of a full-length TAT polypeptide amino acid sequence as disclosed herein, or (b) the complement of the DNA molecule of (a). The described isolated nucleic acid molecule comprising a nucleotide sequence having at least about 80% nucleic acid sequence identity, alternatively at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity, to (a) a DNA molecule comprising the coding sequence of a full-length TAT polypeptide cDNA as disclosed herein, the coding sequence of a TAT polypeptide lacking the signal peptide as disclosed herein, the coding sequence of an extracellular domain of a transmembrane TAT polypeptide, with or without the signal peptide, as disclosed herein or the coding sequence of any other specifically defined fragment of the full-length TAT polypeptide amino acid sequence as disclosed herein, or (b) the complement of the DNA molecule of (a). Also described is an isolated nucleic acid molecule comprising a nucleotide sequence having at least about 80% nucleic acid sequence identity, alternatively at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% nucleic acid sequence identity, to (a) a DNA molecule that encodes the same mature polypeptide encoded by the full-length coding region of any of the human protein cDNAs deposited with the ATCC as disclosed herein, or (b) the complement of the DNA molecule of (a). Also described is an isolated nucleic acid molecule comprising a nucleotide sequence encoding a TAT polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated, or is complementary to such encoding nucleotide sequence, wherein the transmembrane domain(s) of such polypeptide(s) are disclosed herein. Therefore, soluble extracellular domains of the herein described TAT polypeptides are contemplated. Also described are isolated nucleic acid molecules which hybridize to (a) a nucleotide sequence encoding a TAT polypeptide having a full-length amino acid sequence as disclosed herein, a TAT polypeptide amino acid 3d (followed by page 3e) sequence lacking the signal peptide as disclosed herein, an extracellular domain of a transmembrane TAT polypeptide, with or without the signal peptide, as disclosed herein or any other specifically defined fragment of a full-length TAT polypeptide amino acid sequence as disclosed herein, or (b) the complement of the nucleotide sequence of (a). In this regard, fragments of a full-length TAT polypeptide coding sequence, or the complement thereof, are described that may find use as, for example, hybridization probes useful as, for example, diagnostic probes, antisense (followed by page 4) INTELLECTUAL PROPERTY OFFICE OF N.Z t h SEP 2007 oligonucleotide probes, or for encoding fragments of a full-length TAT polypeptide that may optionally encode a polypeptide comprising a binding site for an anti-TAT polypeptide antibody, a TAT binding oligopeptide or other small organic molecule that binds to a TAT polypeptide. Such nucleic acid fragments are usually at least about 5 nucleotides in length, alternatively at least about 6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23, 24,25,26,27,28,29,30,35,40,45,50,55,60,65,70,75,80,85,90,95,100,105,110,115,120,125,130,135,140,145, 150,155,160,165,170,175,180,185,190,195,200,210,220,230,240,250,260,270,280,290,300,310,320,330,340, 350,360,370,380,390,400,410,420,430,440,450,460,470,480,490,500,510,520,530,540,550,560,570,580,590, 600,610,620,630,640,650,660,670,680,690,700,710,720,730,740,750,760,770,780,790,800,810,820,830,840, 850,860,870,880,890,900,910,920,930,940,950,960,970,980,990, or 1000 nucleotides in length, wherein in this context the term "about" means the referenced nucleotide sequence length plus or minus 10% of that referenced length. It is noted that novel fragments of a TAT polypeptide-encoding nucleotide sequence may be determined in a routine manner by aligning the TAT polypeptide-encoding nucleotide sequence with other known nucleotide sequences using any of a number of well known sequence alignment programs and determining which TAT polypeptide-encoding nucleotide sequence fragments) are novel. All of such novel fragments of TAT polypeptide-encoding nucleotide sequences are contemplated herein. Also contemplated are the TAT polypeptide fragments encoded by these nucleotide molecule fragments, preferably those TAT polypeptide fragments that comprise a binding site for an anti-TAT antibody, a TAT binding oligopeptide or other small organic molecule that binds to a TAT polypeptide. Also described are isolated TAT polypeptides encoded by any of the isolated nucleic acid sequences hereinabove identified. Also described is an isolated TAT polypeptide, comprising an amino acid sequence having at least about 80% amino acid sequence identity, alternatively at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity, to a TAT polypeptide having a full-length amino acid sequence as disclosed herein, a TAT polypeptide amino acid sequence lacking the signal peptide as disclosed herein, an extracellular domain of a transmembrane TAT polypeptide protein, with or without the signal peptide, as disclosed herein, an amino acid sequence encoded by any of the nucleic acid sequences disclosed herein or any other specifically defined fragment of a full-length TAT polypeptide amino acid sequence as disclosed herein. Also described is an isolated TAT polypeptide comprising an amino acid sequence having at least about 80% amino acid sequence identity, alternatively at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% amino acid sequence identity, to an amino acid sequence encoded by any of the human protein cDNAs deposited with the ATCC as disclosed herein. Also described is an isolated TAT polypeptide without the N-terminal signal sequence and/or without the initiating methionine and is encoded by a nucleotide sequence that encodes such an amino acid sequence as hereinbefore described. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the TAT polypeptide and recovering the TAT polypeptide from the cell culture. Also described is an isolated TAT polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the TAT polypeptide and recovering 5 the TAT polypeptide from the cell culture. Also described are vectors comprising DNA encoding any of the herein described polypeptides. Host cells comprising any such vector are also provided. By way of example, the host cells may be CHO cells, E. coli cells, or yeast cells. A process for producing any of the herein described polypeptides is further provided and comprises culturing host cells under conditions suitable for 10 expression of the desired polypeptide and recovering the desired polypeptide from the cell culture. Also described are isolated chimeric polypeptides comprising any of the herein described TAT polypeptides fused to a heterologous (non-TAT) polypeptide. Example of such chimeric molecules comprise any of the herein described TAT polypeptides fiised to a heterologous polypeptide such as, for example, an epitope tag sequence or a Fc region of an immunoglobulin. 15 Also described is an antibody which binds, preferably specifically, to any of the above or below described polypeptides. Optionally, the antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, single-chain antibody or antibody that competitively inhibits the binding of an anti-TAT polypeptide antibody to its respective antigenic epitope. Antibodies described may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, 20 for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleoly tic enzyme, or the like. The antibodies described may optionally be produced in CHO cells or bacterial cells and preferably induce death of a cell to which they bind. For diagnostic purposes, the antibodies . may be detectably labeled, attached to a solid support, or the like. Also described are vectors comprising DNA encoding 25 any of the herein described antibodies. Host cell comprising any such vector are also provided. By way of example, the host cells may be CHO cells, E. coli cells, or yeast cells. A process for producing any of the herein described antibodies is further provided and comprises culturing host cells under conditions suitable for expression of the desired antibody and recovering the desired antibody from the cell culture. Also described are oligopeptides ("TAT binding oligopeptides") which bind, 30 preferably specifically, to any of the above or below described TAT polypeptides. Optionally, the TAT binding oligopeptides may be conjugated to a growth inhibitory agent or cytotoxic agent such as atoxin, including, for example, amaytansinoid or calicheamicin, an antibiotic, a radioactive isotope, anucleolytic enzyme, or the like. The TAT binding oligopeptides described ' may optionally be produced in CHO cells or bacterial cells and preferably induce death of a cell to which they bind. For diagnostic purposes, the TAT 35 binding oligopeptides may be detectably labeled, attached to a solid support, or the like. Also described are vectors comprising DNA encoding any of the herein described TAT binding oligopeptides. Host cell comprising any such vector are also provided. 5 By way of example, the host cells may be CHO cells, E. coli cells, or yeast cells. A process for producing any of the herein described TAT binding oligopeptides is further provided and comprises culturing host cells under conditions suitable for expression of the desired oligopeptide and recovering the desired oligopeptide from the cell culture. Also described are small organic molecules ("TAT binding organic 5 molecules") which bind, preferably specifically, to any of the above or below described TAT polypeptides. Optionally, the TAT binding organic molecules may be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The TAT binding organic molecules preferably induce death of a cell to which they bind. For diagnostic purposes, the TAT binding organic molecules 10 may be detectably labeled, attached to a solid support, or the like. Described is a composition of matter comprising a TAT polypeptide as described herein, a chimeric TAT polypeptide as described herein, an anti-TAT antibody as described herein, a TAT binding oligopeptide as described herein, or a TAT binding organic molecule as described herein, in combination with a carrier. Optionally, the carrier is a pharmaceutically acceptable carrier. 15 Also described is an article of manufacture comprising a container and a composition of matter contained within the container, wherein the composition of matter may comprise a TAT polypeptide as described herein, a chimeric TAT polypeptide as described herein, an anti-TAT antibody as described herein, a TAT binding oligopeptide as described herein, or a TAT binding organic molecule as described herein. The article may further optionally comprise a label affixed to the container, or a package insert included 20 with the container, that refers to the use of the composition of matter for the therapeutic treatment or diagnostic detection of a tumor. Also described is the use of a TAT polypeptide as described herein, a chimeric TAT polypeptide as described herein, an anti-TAT polypeptide antibody as described herein, a TAT binding oligopeptide as described herein, or a TAT binding organic molecule as described herein, for the 25 preparation of a medicament useful in the treatment of a condition which is responsive to the TAT polypeptide, f chimeric TAT polypeptide, anti-TAT polypeptide antibody, TAT binding oligopeptide, or TAT binding organic molecule. B. Additional Embodiments Also described is a method for inhibiting the growth of a cell 30 that expresses a TAT polypeptide, wherein the method comprises contacting the cell with an antibody, an oligopeptide or a small organic molecule that binds to the TAT polypeptide, and wherein the binding of the antibody, oligopeptide or organic molecule to the TAT polypeptide causes inhibition of the growth of the cell expressing the TAT polypeptide. In preferred embodiments, the cell is a cancer cell and binding of the antibody, oligopeptide or organic molecule to the TAT polypeptide causes death of the cell expressing the TAT polypeptide. 35 Optionally, the antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, or single-chain antibody. Antibodies, TAT binding oligopeptides and TAT binding organic molecules employed in the methods may optionally be conjugated to a growth inhibitory agent or cytotoxic 6 agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The antibodies and TAT binding oligopeptides employed in the methods of the present invention may optionally be produced in CHO cells or bacterial cells. Also described is a method of therapeutically treating a mammal having a cancerous tumor comprising cells that express a TAT polypeptide, wherein the method comprises 5 administering to the mammal a therapeutically effective amount of an antibody, an oligopeptide or a small organic molecule that binds to the TAT polypeptide, thereby resulting in the effective therapeutic treatment of the tumor. Optionally, the antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, or single-chain antibody. Antibodies, TAT binding oligopeptides and TAT binding organic molecules employed in the methods described may optionally be conjugated to a growth inhibitory agent or cytotoxic 10 agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The antibodies and oligopeptides employed in the methods of the present invention may optionally be produced in CHO cells or bacterial cells. Also described is a method of determining the presence of a TAT polypeptide in a sample suspected of containing the TAT polypeptide, wherein the method comprises 15 exposing the sample to an antibody, oligopeptide or small organic molecule that binds to the TAT polypeptide and determining binding of the antibody, oligopeptide or organic molecule to the TAT polypeptide in the sample, wherein the presence of such binding is indicative of the presence of the TAT polypeptide in the sample. Optionally, the sample may contain cells (which may be cancer cells) suspected of expressing the TAT polypeptide. The antibody, TAT binding oligopeptide or TAT binding organic molecule employed in the method 20 may optionally be detectably labeled, attached to a solid support, or the like. : Also described is a method of diagnosing the presence of a tumor in a mammal, wherein the method comprises detecting the level of expression of a gene encoding a TAT polypeptide (a) in a test sample of tissue cells obtained from said mammal, and (b) in a control sample of known normal non-cancerous cells of the same tissue origin or type, wherein a higher level of expression of the TAT 25 polypeptide in the test sample, as compared to the control sample, is indicative of the presence of tumor in the mammal from which the test sample was obtained. Also described is a method of diagnosing the presence of a tumor in a mammal, wherein the method comprises (a) contacting a test sample comprising tissue cells obtained from the mammal with an antibody, oligopeptide or small organic molecule that binds to a TAT polypeptide and 30 (b) detecting the formation of a complex between the antibody, oligopeptide or small organic molecule and the TAT polypeptide in the test sample, wherein the formation of a complex is indicative of the presence of a tumor in the mammal. Optionally, the antibody, TAT binding oligopeptide or TAT binding organic molecule employed is detectably labeled, attached to a solid support, or the like, and/or the test sample of tissue cells is obtained from an individual suspected of having a cancerous tumor. 3 5 Also described is a method for treating or preventing a cell proliferative disorder associated with altered, preferably increased, expression or activity of a TAT polypeptide, the method comprising administering to a subject in need of such treatment an effective amount of an antagonist 7 of a TAT polypeptide. Preferably, the cell proliferative disorder is cancer and the antagonist of the TAT polypeptide is an anti-TAT polypeptide antibody, TAT binding oligopeptide, TAT binding organic molecule or antisense oligonucleotide. Effective treatment or prevention of the cell proliferative disorder may be a result of direct killing or growth inhibition of cells that express a TAT polypeptide or by antagonizing the cell growth potentiating activity of a TAT polypeptide. Also described is a method of binding an antibody, oligopeptide or small organic molecule to a cell that expresses a TAT polypeptide, wherein the method comprises contacting a cell that expresses a TAT polypeptide with said antibody, oligopeptide or small organic molecule under conditions which are suitable for binding of the antibody, oligopeptide or small organic molecule to said TAT polypeptide and allowing binding therebetween. Also described is the use of (a) a TAT polypeptide, (b) a nucleic acid encoding a TAT polypeptide or a vector or host cell comprising that nucleic acid, (c) an anti-TAT polypeptide antibody, (d) a TAT-binding oligopeptide, or (e) a TAT-binding small organic molecule in the preparation of a medicament useful for (i) the therapeutic treatment or diagnostic detection of a cancer or tumor, or (ii) the therapeutic treatment or prevention of a cell proliferative disorder. Also described is a method for inhibiting the growth of a cancer cell, wherein the growth of said cancer cell is at least in part dependent upon the growth potentiating effects) of a TAT polypeptide (wherein the TAT polypeptide may be expressed either by the cancer cell itself or a cell that produces polypeptide(s) that have a growth potentiating effect on cancer cells), wherein the method comprises contacting the TAT polypeptide with an antibody, an oligopeptide or a small organic molecule that binds to the TAT polypeptide, thereby antagonizing the growth-potentiating activity of the TAT polypeptide and, in turn, inhibiting the growth of the cancer cell. Preferably the growth of the cancer cell is completely inhibited. Even more preferably, binding of the antibody, oligopeptide or small organic molecule to the TAT polypeptide induces the death of the cancer cell. Optionally, the antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, or single-chain antibody. Antibodies, TAT binding oligopeptides and TAT binding organic molecules employed in the. described methods / may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The antibodies and TAT binding oligopeptides employed in the described methods s may optionally be produced in CHO cells or bacterial cells. Also described is a method of therapeutically treating a tumor in a mammal, wherein the growth of said tumor is at least in part dependent upon the growth potentiating effects) of a TAT polypeptide, wherein the method comprises administering to the mammal a therapeutically effective amount of an antibody, an oligopeptide or a small organic molecule that binds to the TAT polypeptide, thereby antagonizing the growth potentiating activity of said TAT polypeptide and resulting in the effective therapeutic treatment of the tumor. Optionally, the antibody is a monoclonal antibody, antibody fragment, chimeric antibody, humanized antibody, or single-chain antibody. Antibodies, TAT binding oligopeptides and TAT binding organic molecules employed may optionally be conjugated to a growth inhibitory agent or cytotoxic agent such as a toxin, including, for example, a maytansinoid or calicheamicin, 8 an antibiotic, a radioactive isotope, a nucleolytic enzyme, or the like. The antibodies and oligopeptides employed in the methods of the present invention may optionally be produced in CHO cells or bacterial cells. C. Further Additional Embodiments 5 Described are: 1. Isolated nucleic acid having a nucleotide sequence that has at least 80% nucleic acid sequence identity to: ....... (a) a DNA molecule encoding the amino acid sequence shown in any one of Figures 4-6 (SEQ ID NOS:4- «); 10 (b) a DNA molecule encoding the amino acid sequence shown in any one of Figures 4-6 (SEQ ID NOS:4- 6), lacking its associated signal peptide; (c) a DNA molecule encoding an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) a DNA molecule encoding an extracellular domain of the polypeptide shown in any one of Figures 4-6 15 (SEQ ID NOS:4-6), lacking its associated signal peptide; (e) the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3); (f) the full-length coding region of the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3); or (g) the complement of (a), (b), (c), (d), (e) or (f). 20 2. Isolated nucleic acid having: (a) a nucleotide sequence that encodes the amino acid sequence shown in any one of Figures 4-6 (SEQ EDNOS-.4-6); (b) a nucleotide sequence that encodes the amino acid sequence shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; 25 (c) a nucleotide sequence that encodes an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) a nucleotide sequence that encodes an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (e) the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3); 30 (f) the fidl-length coding region of the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3); or (g) the complement of (a), (b), (c), (d), (e) or (f). 3. Isolated nucleic acid that hybridizes to: (a) a nucleic acid that encodes the amino acid sequence shown in any one of Figures 4-6 (SEQ ID NOS:4- 35 6); (b) a nucleic acid that encodes the amino acid sequence shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; 9 (c) a nucleic acid that encodes an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) a nucleic acid that encodes an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (e) the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3); (f) the full-length coding region of the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3); or (g) the complement of (a), (b),(c), (d), (e) or (f). • 4. The nucleic acid of Claim 3, wherein the hybridization occurs under stringent conditions. 5. The nucleic add of Claim 3 which is at least about 5 nucleotides in length. 6. An expression vector comprising the nucleic acid of Claim 1,2 or 3. 7. The expression vector of Claim 6, wherein said nucleic acid is operably linked to control sequences recognized by a host cell transformed with die vector. 8. A host cell comprising the expression vector of Claim 7. 9. The host cell of Claim 8 which is a CHO cell, an E. coli cell or a yeast cell. 10. A process for producing a polypeptide comprising culturing the host cell of Claim 8 under conditions suitable for expression of said polypeptide and recovering said polypeptide from the cell culture. 11. An isolated polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQIDNOS:4-6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3). 12. An isolated polypeptide having: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ED NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ IDNOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal 'peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; 10 (c) an amino acid sequence encoded by the nucleotide sequence shown in any one of Figures 1-3 (SEQ DDNOS:l-3);or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3). 13. A chimeric polypeptide comprising the polypeptide of Claim 11 or 12 fused to a heterologous 5 polypeptide. 14. The chimeric polypeptide of Claim 13, wherein said heterologous polypeptide is an epitope tag sequence or an Fc region of an immunoglobulin. ------ 15. An isolated antibody that binds to a polypeptide having at least 80% amino acid sequence identifyto: 10 (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal ^ peptide; (c) an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; 15 (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ IDNOS:4-6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQIDNOS:l-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one 20 ofFigures 1-3 (SEQ ID NOS:l-3). 16. An isolated antibody that binds to a polypeptide having: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; 25 (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ 30 ID NOS:l-3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3). 17. The antibody of Claim 15 or 16 which is a monoclonal antibody. 18 35 19 20 21 The antibody of Claim 15 or 16 which is an antibody fragment The antibody of Claim 15 or 16 which is a chimeric or a humanized antibody. The antibody of Claim 15 or 16 which is conjugated to a growth inhibitory agent The antibody of Claim 15 or 16 which is conjugated to a cytotoxic agent. 11 22. Hie antibody of Claim 21, wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 23. The antibody of Claim 21, wherein the cytotoxic agent is a toxin. 24. The antibody of Claim 23, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 5 25. The antibody of Claim 23, wherein the toxin is a maytansinoid. 26. The antibody of Claim 15 or 16 which is produced in bacteria. 27. The antibody of Claim 15 or 16 which is produced in CHO cells. 28. Hie antibody of Claim 15 or 16 which induces death of a cell to which it binds. 29. The antibody of Claim 15 or 16 which is detectably labeled. 10 30. An isolated nucleic add having a nucleotide sequence that encodes the antibody of Claim 15 or 16. 31. An expression vector comprising the nucleic add of Claim 30 operably linked to control sequences recognized by a host cell transformed with the vector. 32. A host cell comprising the expression vector of Claim 31. 15 33. Hie host cell of Claim 32 which is a CHO cell, an £.coli cell or a yeast cell 34. A process for producing an antibody comprising culturing the host cell of Claim 32 under conditions suitable for expression of said antibody and recovering said antibody from the cell culture. 35. An isolated oligopeptide that binds to a polypeptide having at least 80% amino acid sequence identity to: 20 (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its assodated signal peptide; 25 (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking | its assodated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ IDNOS: 1-3); ' or (f) a polypeptide encoded by the full-length, coding region of the nucleotide sequence shown in any one 30 ofFigures 1-3 (SEQ ID NOS:l-3). 36. An isolated oligopeptide that binds to a polypeptide having: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; 35 (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; 12 (d) an amino acid sequence of an extracellular domain of die polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (e) aa amino acid sequence encoded by the nucleotide sequence shown in any one of Figures 1-3 (SEQ EDNOS:l-3);or (f) an amino acid sequence encoded by the full-length coding region of die nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3). 37. The oligopeptide of Claim 35 or 36 which is conjugated to a growth inhibitory agent 38. " The oligopeptide of Claim 35 or 36 which is conjugated to a cytotoxic agent 39. The oligopeptide of Claim 38, wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 40. The oligopeptide of Claim 38, wherein the cytotoxic agent is a toxin. 41. The oligopeptide of Claim 40, wherein the toxin is selected from die group consisting of maytansinoid and calicheamicin. 42. The oligopeptide of Claim 40, wherein the toxin is a maytansinoid. 43. The oligopeptide of Claim 35 or 36 which induces death of a cell to which it binds. 44. The oligopeptide of Claim 35 or 36 which is detectably labeled. 45. A TAT binding organic molecule that binds to a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ED NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ED NOS:4-6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQIDNOS:l-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ JD NOS.-1-3). 46. The organic molecule of Claim 45 that binds to a polypeptide having: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ED NOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; 13 (c) an amino acid sequence encoded by the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS:l-3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3). 47. The organic molecule of Claim 45 or 46 which is conjugated to a growth inhibitory agent 48. The organic molecule of Claim 45 or 46 which is conjugated to a cytotoxic agent 49. The organic molecule of Claim 48, wherein the cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 50. The organic molecule of Claim 48, wherein the cytotoxic agent is a toxin. 51. The organic molecule of Claim 50, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 52. The organic molecule of Claim 50, wherein the toxin is a maytansinoid. 53. The organic molecule of Claim 45 or 46 which induces death of a cell to which it binds. 54. The organic molecule of Claim 45 or 46 which is detectably labeled. 55. A composition of matter comprising: (a) the polypeptide of Claim 11; (b) the polypeptide of Claim 12; (c) the chimeric polypeptide of Claim 13; (d) the antibody of Claim 15; (e) the antibody of Claim 16; © the oligopeptide of Claim 35; (g) the oligopeptide of Claim 36; 00 the TAT binding organic molecule of Claim 45; or (i) the TAT binding organic molecule of Claim 46; in combination with a carrier. 56. The composition of matter of Claim 55, wherein said carrier is a pharmaceutically acceptable 57. An article of manufacture comprising: (a) a container; and (b) the composition of matter of Claim 55 contained within said container. 58. The article of manufacture of Claim 57 further comprising a label affixed to said container, or a package insert included with said container, referring to the use of said composition of matter for die therapeutic treatment of or the diagnostic detection of a cancer. 59. A method of inhibiting the growth of a cell that expresses a protein having at least 80% ammo acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; 14 (c) 811 extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SBQID NOS:4-6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3), said method comprising contacting said cell with an antibody, oligopeptide or organic molecule that binds to said protein, the binding of said antibody, oligopeptide or organic molecule to said protein thereby causing an inhibition of growth of said cell. 60. The method of Claim 59, wherein said antibody is a monoclonal antibody. 61. The method of Claim 59, wherein said antibody is an antibody fragment. 62. The method of Claim 59, wherein said antibody is a chimeric or a humanized antibody. 63. Hie method of Claim 59, wherein said antibody, oligopeptide or organic molecule is conjugated to a growth inhibitory agent 64. The method of Claim 59, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent 65. The method of Claim 64, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 66. The method of Claim 64, wherein the cytotoxic agent is a toxin. 67. The method of Claim 66, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 68. • The method of Claim 66, wherein the toxin is a maytansinoid. 69. The method of Claim 59, wherein said antibody is produced in bacteria. 70. The method of Claim 59, wherein said antibody is produced in CHO cells. 71. The method of Claim 59, wherein said cell is a cancer cell. 72. The method of Claim 71, wherein said cancer cell is further exposed to radiation treatment or a chemotherapeutic agent 73. The method of Claim71, wherein said cancer cell is selected from the group consisting of abreast cancer cell, a colorectal cancer cell, a lung cancer cell, an ovarian cancer cell, a central nervous system cancer cell, a liver cancer cell, a bladder cancer cell, a pancreatic cancer cell, a cervical cancer cell, a melanoma cell and a leukemia cell. 74. The method of Claim 71, wherein said protein is more abundantly expressed by said cancer cell as compared to a normal cell of the same tissue origin. 75. The method of Claim 59 which causes the death of said cell. 76. The method of Claim 59, wherein said protein has: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); 15 (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ IDNOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 ) (SEQ ID NOS:4-6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQIDNOS:4-6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ IDNOS:l-3);or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3). 77. A method of therapeutically treating a mammal having a cancerous tumor comprising cells that express a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: I -3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ED NOS: 1-3), said method comprising administering to said mammal a therapeutically effective amount of an antibody, oligopeptide or organic molecule that binds to said protein, thereby effectively treating said mammal. 78. The method of Claim 77, wherein said antibody is a monoclonal antibody. 79. Hie method of Claim 77, wherein said antibody is an antibody fragment 80. The method of Claim 77, wherein said antibody is a chimeric or a humanized antibody. 81. The method of Claim 77, wherein said antibody, oligopeptide or organic molecule is conjugated to a growth inhibitory agent 82. The method of Claim 77, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent 83. The method of Claim 82, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 84. The method of Claim 82, wherein the cytotoxic agent is a toxin. 85. The method of Claim 84, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 86. The method of Claim 84, wherein the toxin is a maytansinoid. 16 87. The method of Claim 77, wherein said antibody is produced in bacteria. 88. The method of Claim 77, wherein said antibody is produced in CHO cells. 89. The method of Claim 77, wherein said tumor is further exposed to radiation treatment or a chemotherapeutic agent. 90. The method of Claim 77, wherein said tumor is a breast tumor, a colorectal tumor, a lung tumor, an ovarian tumor, a central nervous system tumor, a liver tumor, a bladder tumor, a pancreatic tumor, or a cervical tumor. 91. The method of Claim 77, wherein said protein is more abundantly expressed by the cancerous cells of said tumor as compared to a normal cell of the same tissue origin. 92. The method of Claim 77, wherein said protein has: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in any one of Figures 1-3 (SEQ ID NOS: 1-3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3). 93. A method of determining the presence of a protein in a sample suspected of containing said protein, wherein said protein has at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS :4-6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3), said method comprising exposing said sample to an antibody, oligopeptide or organic molecule that binds to said protein and determining binding of said antibody, oligopeptide or organic molecule to said protein in said sample, wherein binding of the antibody, oligopeptide or organic molecule to said protein is indicative of the presence of said protein in said sample. 17 94. The method of Claim 93, wherein said sample comprises a cell suspected of expressing said protein. 95. The method of Claim 94, wherein said cell is a cancer cell. 96. The method of Claim 93, wherein said antibody, oligopeptide or organic molecule is detectably labeled. 5 97. The method of Claim 93, wherein said protein has: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 10 (SEQ ID NOS:4-6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4~6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or 15 (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3). 98. A method of diagnosing the presence of a tumor in a mammal, said method comprising determining the level of expression of a gene encoding a protein having at least 80% amino acid sequence identity to: 20 (a) the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; 25 (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ED NOS:4-6), lacking its associated signal peptide; (e) apolypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one 3 0 ofFigures 1 -3 (SEQ ID NOS: 1 -3), in a test sample of tissue cells obtained from said mammal and in a control sample of known normal cells of the same tissue origin, wherein a higher level of expression of said protein in the test sample, as compared to the control sample, is indicative of the presence of tumor in the mammal from which the test sample was obtained. 99. The method of Claim 98, wherein the step of determining the level of expression of a gene 3 5 encoding said protein comprises employing an oligonucleotide in an in situ hybridization or RT-PCR analysis. 100. The method of Claim 98, wherein the step determining the level of expression of a gene encoding said protein comprises employing an antibody in an immunohistochemistry or Western blot analysis. 18 101. The method of Claim 98, wherein said protein has: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequencer (e) an amino acid sequence encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS*.l-3). 102. A method of diagnosing the presence of a tumor in a mammal, said method comprising contacting a test sample of tissue cells obtained from said mammal with an antibody, oligopeptide or organic molecule that binds to a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (e) apolypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ IDNOS:l-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3), and detecting the formation of a complex between said antibody, oligopeptide or organic molecule and said protein in the test sample, wherein the formation of a complex is indicative of the presence of a tumor in said mammal. 103. The method of Claim 102, wherein said antibody, oligopeptide or organic molecule is detectably labeled. 104. The method of Claim 102, wherein said test sample of tissue cells is obtained from an individual suspected of having a cancerous tumor. 105. The method of Claim 102, wherein said protein has: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; 19 (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3). 106. A method for treating or preventing a cell proliferative disorder associated with increased expression or activity of a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6(SEQ ID NOS:4-6), lacking its associated signal peptide; (e) apolypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3), said method comprising administering to a subject in need of such treatment an effective amount of an antagonist of said protein, thereby effectively treating or preventing said cell proliferative disorder. 107. The method of Claim 106, wherein said cell proliferative disorder is cancer. 108. The method of Claim 106, wherein said antagonist is an anti-TAT polypeptide antibody, TAT binding oligopeptide, TAT binding organic molecule or antisense oligonucleotide. 109. A method of binding an antibody, oligopeptide or organic molecule to a cell that expresses a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS :4-6), lacking its associated signal peptide; (e) apolypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS:l-3), said method comprising contacting said cell with an antibody, oligopeptide or organic molecule that binds to said protein and allowing the binding of the antibody, oligopeptide or organic 20 molecule to said protein to occur, thereby binding said antibody, oligopeptide or organic molecule to said cell. 110. The method of Claim 109, wherein said antibody is a monoclonal antibody. 111. Hie method of Claim 109, wherein said antibody is an antibody fragment. 112. Hie method of Claim 109, wherein said antibody is a chimeric or a humanized antibody. 113. The method of Claim 109, wherein said antibody, oligopeptide or organic molecule is conjugated to a growth inhibitory agent 114. The method of Claim 109, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent. .. .. 115. The method of Claim 114, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 116. The method of Claim 114, wherein the cytotoxic agent is a toxin. ♦ 117. The method of Claim 116, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 118. The method of Claim 116, wherein the toxin is a maytansinoid. 119. The method of Claim 109, wherein said antibody is produced in bacteria. 120. Hie method of Claim 109, wherein said antibody is produced in CHO cells. 121. The method of Claim 109, wherein said cell is a cancer cell. 122. The method of Claim 121, wherein said cancer cell is further exposed to radiation treatment or a chemotherapeutic agent 123. The method of Claim 121, wherein said cancer cell is selected from the group consisting of a breast cancer cell, a colorectal cancer cell, a lung cancer cell, an ovarian cancer cell, a central nervous system cancer cell, a liver cancer cell, abladder cancer cell, a pancreatic cancer cell, a cervical cancer cell, a melanoma cell and a leukemia cell. 124. The method of Claim 123, wherein said protein is more abundantly expressed by said cancer cell as compared to a normal cell of the same tissue origin. 125. The method of Claim 109 which causes the death of said cell. 126. Use ofa nucleic acid as claimed in any of Claims 1 to 5 or 30 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 127. Use of a nucleic acid as claimed in any of Claims 1 to 5 or 30 in the preparation of a medicament for treating a tumor. 128. Use of a nucleic acid as claimed in any of Claims 1 to 5 or 30 in the preparation of a medicament for treatment or prevention ofa cell proliferative disorder. 129. Use of an expression vector as claimed in any of Claims 6, 7 or 31 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 130. Use of an expression vector as claimed in any of Claims 6, 7 or 31 in the preparation of medicament for treating a tumor. 131. Use of an expression vector as claimed in any of Claims 6, 7 or 31 in die preparation of a medicament for treatment or prevention of a cell proliferative disorder. 21 132. Use ofa host cell as claimed in any of Claims 8,9,32, or 33 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 133. Use of a host cell as claimed in any of Claims 8,9,32 or 33 in the preparation of a medicament for treating a tumor. 134. Use of a host cell as claimed in any of Claims 8,9,32 or 33 in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. 135. Use ofa polypeptide as claimed in any of Claims 11 to 14 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 136. Use ofa polypeptide as claimed in any of Claims 11 to 14 in the preparation of a medicament for treating a tumor. 137. Use of a polypeptide as claimed in any of Claims 11 to 14 in the preparation ofa medicament for treatment or prevention of a cell proliferative disorder. 138. Use of an antibody as claimed in any of Claims 15 to 29 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 139. Use of an antibody as claimed in any of Claims 15 to 29 in the preparation of a medicament for treating a tumor. 140. Use of an antibody as claimed in any of Claims 15 to 29 in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. 141. Use of an oligopeptide as claimed in any of Claims 35 to 44 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 142. Use of an oligopeptide as claimed in any of Claims 35 to 44 in the preparation of a medicament for treating a tumor. 143. Use of an oligopeptide as claimed in any of Claims 35 to 44 in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. 144. Use of a TAT binding organic molecule as claimed in any of Claims 45 to 54 in tire preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 145. Use of a TAT binding organic molecule as claimed in any of Claims 45 to 54 in the preparation of a medicament for treating a tumor. 146. Use of a TAT binding organic molecule as claimed in any of Claims 45 to 54 in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. 147. Use of a composition of matter as claimed in any of Claims 55 or 56 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 148. Use of a composition of matter as claimed in any of Claims 55 or 56 in the preparation of a medicament for treating a tumor. 149. Use of a composition of matter as claimed in any of Claims 55 or 56 in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. 150. Use of an article of manufacture as claimed in any of Claims 57 or 58 in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 22 151. Use of an article of manufacture as claimed in any of Claims 57 or 58 in the preparation ofa medicament for treating a tumor. 152. Use of an article of manufacture as claimed in any of Claims 57 or 58 in the preparation of a medicament for treatment or prevention of a cell proliferative disorder. 153. A method for inhibiting the growth of a cell, wherein the growth of said cell is at least in part dependent upon a growth potentiating effect of a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in "any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated-signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ IDNOS:4-6), lacking its associated signal peptide; (e) apolypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) a polypeptide encoded by the foil-length coding region of the nucleotide sequence shown in any one of Figutes 1-3 (SEQ ID NOS: 1-3), said method comprising contacting said protein with an antibody, oligopeptide or organic molecule that binds to said protein, there by inhibiting the growth of said cell. 154. The method of Claim 153, wherein said cell is a cancer cell. 155. The method of Claim 153, wherein said protein is expressed by said cell. 156. The method of Claim 153, wherein the binding of said antibody, oligopeptide or organic molecule to said protein antagonizes a cell growth-potentiating activity of said protein. 157. ThemethodofClaiml53, whereinthebindingofsaidantibody, oligopeptide or oiganic molecule to said protein induces the death of said cell. 158. The method of Claim 153, wherein said antibody is a monoclonal antibody. 159. The method of Claim 153, wherein said antibody is an antibody fragment. 160. The method of Claim 153, wherein said antibody is a chimeric or a humanized antibody. 161. The method of Claim 153, wherein said antibody, oligopeptide or oiganic molecule is conjugated to a growth inhibitory agent. 162. The method of Claim 153, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent 163. The method of Claim 162, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 164. The method of Claim 162, wherein the cytotoxic agent is a toxin. 165. The method of Claim 164, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 166. The method of Claim 164, wherein the toxin is a maytansinoid. 167. The method of Claim 153, wherein said antibody is produced in bacteria. 23 168. The method of Claim 153, wherein said antibody is produced in CHO cells. 169. The method of Claim 153, wherein said protein has: (a) the amino acid sequence shown in any one of Figures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; 5 (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; ' (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one of Figures-4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; • (e) an amino acid sequence encoded by the nucleotide sequence shown in any one of Figures 1-3 (SEQ 10 ID NOS: 1-3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown ^ in any one ofFigures 1-3 (SEQ ID NOS:l-3). * 170. A method of therapeutically treating a tumor in a mammal, wherein the growth of said tumor is at least in part dependent upon a growth potentiating effect of a protein having at least 80% ammo acid sequence 15 identity to: (a) the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the polypeptide shown in any one of Figures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS.-4-6), with 20 its associated signal peptide; (d) an extracellular domain ofthe polypeptide shown in any one ofFigures 4-6 (SEQIDNOS:4-6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or 25 (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3), said method comprising contacting said protein with an antibody, oligopeptide or oiganic molecule that binds to said protein, thereby effectively treating said tumor. . 171. The method of Claim 170, wherein said protein is expressed by cells of said tumor. 172. The method of Claim 170, wherein the binding of said antibody, oligopeptide or organic molecule 30 to said protein antagonizes a cell growth-potentiating activity of said protein. 173. The method of Claim 170, wherein said antibody is a monoclonal antibody. 174. The method of Claim 170, wherein said antibody is an antibody fragment 175. The method of Claim 170, wherein said antibody is a chimeric or a humanized antibody. 176. The method of Claim 170, wherein said antibody, oligopeptide or oiganic molecule is conjugated 35 to a growth inhibitoiy agent. 177. The method of Claim 170, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent 24 178. The method of Claim 177, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 179. The method of Claim 177, wherein the cytotoxic agent is a toxin. 180. The method of Claim 179, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 181. The method of Claim 179, wherein the toxin is a maytansinoid. 182. The method of Claim 170, wherein said antibody is produced in bacteria. 183. The method ofClaim 170, wherein said antibody is produced in CHO cells. 184. The method of Claim 170, wherein said protein has: (a) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6); (b) the amino acid sequence shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one ofFigures 4-6 (SEQ ID NOS:4-6), lacking its associated signal peptide sequence; (e) an amino add sequence encoded by the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in any one ofFigures 1-3 (SEQ ID NOS: 1-3). 185. A method of therapeutically treating a psoriatic condition in a mammal, said method comprising administering to said mammal a therapeutically effective amount of an antagonist antibody, antagonist oligopeptide or antagonist organic molecule that binds to a TAT394 polypeptide, thereby effectively treating said condition. 186. The method of Claim 185, wherein said antibody is a monoclonal antibody. 187. The method of Claim 185, wherein said antibody is an antibody fragment. 188. The method of Claim 185, wherein said antibody is a chimeric or a humanized antibody. 189. The method of Claim 185, wherein said antibody, oligopeptide or organic molecule is conjugated to a growth inhibitory agent 190. The method of Claim 185, wherein said antibody, oligopeptide or oiganic molecule is conjugated to a cytotoxic agent. 191. The method of Claim 190, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 192. The method of Claim 190, wherein the cytotoxic agent is a toxin. 193. The method of Claim 192, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 194. The method of Claim 192, wherein the toxin is a maytansinoid. 195. The method of Claim 185, wherein said antibody is produced in bacteria. 25 196. The method of Claim 185, wherein said antibody is produced in CHO cells. 197. A method of therapeutically treating apsoriatic condition in a mammal, said method comprising administering to said mammal a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 4 (SEQ ID NO:4); (b) the polypeptide shown in Figure 4 (SEQ ID NO:4), lacking its associated signal peptide; 5 (c) an extracellular domain of the polypeptide shown inFigure 4 (SEQ ID NO:4), with its associated signal peptide; (d) ah extracellular domain of the polypeptide shown in Figure 4 (SEQ D>NO:4), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 1 (SEQ ED NO:l); or 10 (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 1 (SEQ ID NO:l), thereby effectively treating said condition. 198. The method of Claim 197, wherein said polypeptide has: (a) the amino acid sequence shown in Figure 4 (SEQ ID NO:4); (b) the amino acid sequence shown in Figure 4 (SEQ ID NO:4), lacking its associated signal peptide 15 sequence; (c) an amino acid sequence of an extracellular domainofthepolypeptideshowninFigure4 (SEQ IDNO:4), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in Figure 4 (SEQ ID NO:4), lacking its associated signal peptide sequence; 20 (e) an amino acid sequence encoded by the nucleotide sequence shown in Figure 1 (SEQ ID NO:l); or (f) an amino acid sequence encoded by die full-length coding region of the nucleotide sequence shown inFigure 1 (SEQ ID NO:l). Yet further embodiments of the present invention will be evident to the skilled artisan upon a reading of the present specification. 25 BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a nucleotide sequence (SEQ ID NO:l)ofaTAT393 cDNA, wherein SEQ IDNO:l isaclone designated herein as "DNA64888-1542". Figure2 shows anucleotide sequence (SEQ IDNO:2) of aTAT394 cDNA, wherein SEQIDNO:2 is aclone 30 designated herein as "DNA64889-1541". Figure 3 shows anucleotide sequence (SEQIDNO:3) of aTAT395 cDNA, wherein SEQ IDNO:3 is aclone designated herein as "DNA57700-1408". Figure 4 shows the amino acid sequence (SEQ ID NO:4) derived from the coding sequence of SEQ ID NO:l shown in Figure 1. 35 Figure 5 shows the amino acid sequence (SEQ ID NO:5) derived from the coding sequence of SEQ ID NO:2 shown in Figure 2. 26 Figure 6 shows the amino acid sequence (SEQ ID NO:6) derived from the coding sequence of SEQ ID NO:3 shown in Figure 3. raTTATT RT) DESCRIPTION OF THE PREFERRED EMBODIMENTS I. Definitions 5 The terms "TAT polypeptide" and "TAT" as used herein and when immediately followed by a numerical designation, refer to various polypeptides, wherein the complete designation (i.e.,TAT/number) refers to specific polypeptide sequences as described herein. The terms "TAT/number polypeptide" and "TAT/number" wherein the term "number" is provided as an actual numerical designation as used herein encompass native sequence polypeptides, polypeptide variants and fragments of native sequence polypeptides and polypeptide variants 10 (which are further defined herein). The TAT polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic | methods. The term "TAT polypeptide" refers to each individual TAT/number polypeptide disclosed herein. All disclosures in this specification which refer to the "TAT polypeptide" refer to each of the polypeptides individually as well as jointly. For example, descriptions of the preparation o£ purification o£ derivation of, 15 formation of antibodies to or against, formation of TAT binding oligopeptides to or against, formation of TAT binding organic molecules to or against, administration of, compositions containing, treatment of a disease with, etc., pertain to each polypeptide of the invention individually. The term "TAT polypeptide" also includes variants of the TAT/number polypeptides disclosed herein. A "native sequence TAT polypeptide" comprises a polypeptide having the same amino acid sequence 20 as the corresponding TAT polypeptide derived from nature. Such native sequence TAT polypeptides can be isolated from nature or can be produced by recombinant or synthetic means. The term "native sequence TAT polypeptide" specifically encompasses naturally-occurring truncated or secreted forms of the specific TAT polypeptide (e.g., an extracellular domain sequence), naturally-occurring variant forms (e.g., alternatively spliced forms) and naturally-occurring allelic variants of the polypeptide. In certain embodiments of the invention, the 25 native sequence TAT polypeptides disclosed herein are mature or foil-length native sequence polypeptides | comprising the foil-length amino acids sequences shown in the accompanying figures. Start and stop codons (if indicated) are shown in bold font and underlined in the figures. Nucleic acid residues indicated as "N" in the accompanying figures are any nucleic acid residue. However, while the TAT polypeptides disclosed in the accompanying figures are shown to begin with methionine residues designated herein as amino acid position 1 30 in the figures, it is conceivable and possible that other methionine residues located either upstream or downstream from the amino acid position 1 in the figures may be employed as the starting amino acid residue for the TAT polypeptides. The TAT polypeptide "extracellular domain" or "ECD" refers to a form of the TAT polypeptide which is essentially free of the transmembrane and cytoplasmic domains. Ordinarily, a TAT polypeptide BCD will have less 35 than 1% of such transmembrane and/or cytoplasmic domains and preferably, will have less than 0.5% of such domains. It will be understood that any transmembrane domains identified for the TAT polypeptides of the present invention are identified pursuant to criteria routinely employed in the art for identifying that type of 27 hydrophobic domain. The exact boundaries of a transmembrane domain may vary but most likely by no more than about 5 amino acids at either end of the domain as initially identified herein. Optionally, therefore, an extracellular domain of a TAT polypeptide may contain from about 5 or fewer amino acids on either side of the transmembrane domain/extracellular domain boundary as identified in the Examples or specification and such polypeptides, with or without the associated signal peptide, and nucleic acid encoding them, are contemplated by the present invention. The approximate location of the "signal peptides" of the various TAT polypeptides disclosed herein may be shown in the present specification and/or the accompanying figures.- It is noted, however, that the C-tetminal boundary of a signal peptide may vary, but most likely by no more than about 5 amino acids on either side of the signal peptide C-terminal boundary as initially identified herein, wherein the C-teiminal boundary of the signal peptide may be identified pursuant to criteria routinely employed in the art for identifying that type of amino add sequence element (e.g., Nielsen et aL, ProtEne. 10:1-6(1997) and vonHeinie et al.. Nucl. Acids. Res. 14:4683-4690 (1986)). Moreover, it is also recognized that, in some cases, cleavage of a signal sequence from a secreted polypeptide is not entirely uniform, resulting in more than one secreted spedes. These mature polypeptides, where the signal peptide is cleaved within no more than about 5 amino acids on dther side of the C-terminal boundary of the signal peptide as identified herein, and the polynucleotides encoding them, are contemplated by the present invention. "TAT polypeptide variant" means a TAT polypeptide, preferably an active TAT polypeptide, as defined herein having at least about 80% amino acid sequence identity with a full-length native sequence TAT polypeptide sequence as disclosed herein, a TAT polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a TAT polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length TAT polypeptide sequence as disclosed herein (such as those encoded by a nucleic acid that represents only a portion of the complete coding sequence for a full-length TAT polypeptide). Such TAT polypeptide variants include, for instance, TAT polypeptides wherein one or more amino acid residues are added, or deleted, at the N- or C-terminus of the full-length native amino add sequence. Ordinarily, a TAT polypeptide variant will have at least about 80% amino acid sequence identity, alternatively at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or99% amino acid sequence identity, to a full-length native sequence TAT polypeptide sequence as disclosed herein, a TAT polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a TAT polypeptide, with or without the signal peptide, as disclosed herein or any other specifically defined fragment of a foil-length TAT polypeptide sequence as disclosed herein. Ordinarily, TAT variant polypeptides are at least about 10 amino adds in length, alternatively at least about20,30,40,50,60,70,80,90,100,110,120,130,140,150,160,170,180,190,200,210,220, 230,240,250,260,270,280,290,300,310,320,330,340,350,360,370,380,390,400,410,420,430,440,450,460,470, 480,490,500,510,520,530,540,550,560,570,580,590,600 amino acids inlength, or more. Optionally, TAT variant polypeptides will have no more than one conservative amino acid substitution as compared to the native TAT polypeptide sequence, alternatively no more than 2,3,4,5, 6,7,8,9, or 10 conservative amino acid substitution as compared to the native TAT polypeptide sequence. 28 "Percent (%) amino acid sequence identity" with respect to the TAT polypeptide sequences identified herein is defined as the percentage of amino acid residues in a candidate sequence that axe identical with the amino acid residues in die specific TAT polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can 5 be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2, wherein the 10 complete source code for the ALIGN-2 program is provided in Table 1 below. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shown in Table 1 below has been filed with user documentation in die U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc., South SanFrancisco, California or may be compiled from the source code provided in Table 1 below. The ALIGN-2 IS program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D. All sequence comparison parameters are set by die ALIGN-2 program and do not vary. In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence 20 identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is die number of amino acid residues scored as identical matches by the sequence alignment program 25 AIIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino add sequence B, the % amino acid sequence identify of A to B will not equal the % amino acid sequence identity of B to A. As examples of % amino acid sequence identity calculations using this method, Tables 2 and 3 demonstrate how to calculate the % amino acid sequence identity of the amino acid sequence designated 30 "Comparison Protein" to the amino acid sequence designated "TAT", wherein "TAT" represents the amino acid sequence of a hypothetical TAT polypeptide of interest, "Comparison Protein" represents the amino acid sequence of a polypeptide against which the 'TAT" polypeptide of interest is being compared, and "X, "Y" and "Z" each represent different hypothetical amino acid residues. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using 35 the ALIGN-2 computer program. "TAT variant polynucleotide" or 'TAT variant nucleic acid sequence" means a nucleic acid molecule which encodes a TAT polypeptide, preferably an active TAT polypeptide, as defined herein and which has at least 29 about 80% nucleic acid sequence identity with a nucleotide acid sequence encoding a full-length native sequence TA? polypeptide sequence as disclosed herein, a full-length native sequence TAT polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a TAT polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length TAT polypeptide sequence as disclosed herein (such as those encoded by a nucleic acid that represents only a portion of the complete coding sequence for a full-5 length TAT polypeptide). Ordinarily, a TAT variant polynucleotide will have at least about 80% nucleic acid sequence identity, alternatively at least about 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,"98%, or 99% nucleic acid sequence identity with a nucleic acid sequence encoding a full-length native sequence TAT polypeptide sequence as disclosed herein, a full-length native sequence TAT polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a TAT polypeptide, 10 with or without the signal sequence, as disclosed herein or any other fragment of a full-length TAT polypeptide sequence as disclosed herein. Variants do not encompass the native nucleotide sequence. ^ Ordinarily, TAT variant polynucleotides are at least about 5 nucleotides in length, alternatively at least ^ about6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,35,40,45,50,55,60,65,70, 75,80,85,90,95,100,105,110,115,120,125,130,135,140,145,150,155,160,165,170,175,180,185,190,195,200, 15 210,220,230,240,250,260,270,280,290,300,310,320,330,340,350,360,370,380,390,400,410,420,430,440,450, 460,470,480,490,500,510,520,530,540,550,560,570,580,590,600,610,620,630,640,650,660,670,680,690,700, 710,720,730,740,750,760,770,780,790,800,810,820,830,840,850,860,870,880,890,900,910,920,930,940,950, 960,970,980,990, or 1000 nucleotides in length, wherein in this context the term "about" means the referenced nucleotide sequence length plus or minus 10% of that referenced length. 20 "Percent (%) nucleic acid sequence identity" with respect to TAT-encoding nucleic acid sequences identified herein is defined as the percentage of nucleotides in a candidate sequence that are identical with the nucleotides in the TAT nucleic acid sequence of interest, after aligning the sequences and introducing gaps, if necessaiy, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, 25 using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. ^ For purposes herein, however, % nucleic acid sequence identity values are generated using the sequence comparison computer program AIIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Table 1 below. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shown in Table 1 below has been filed with user documentation in the U.S. Copyright Office, 30 WashingtonD.C., 20559, where it is registered under U.S. CopyrightRegistrationNo. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, California or may be compiled from the source code provided in Table 1 below. The ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vaty. 35 In situations where ALIGN-2,is employed for nucleic acid sequence comparisons, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid 30 sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z where W is the number of nucleotides scored as identical matches by the sequence alignment program ALIGN-2 5 in that program's alignment of C and D, and where Z is the total number of nucleotides in D, It will be appreciated that where the length of nucleic acid sequence C is not equal to die length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identify of D to C. As examples of % nucleic acid sequence identity calculations, Tables 4 and 5, demonstrate how to calculate the % nucleic acid sequence identity of the nucleic acid sequence designated "Comparison DNA" to the nucleic acid sequence 10 designated "TAT-DNA", wherein. 'TAT-DNA" represents a hypothetical TAT-encoding nucleic acid sequence of interest, "Comparison DNA" represents the nucleotide sequence of a nucleic acid molecule against which the "TAT-DNA" nucleic acid molecule of interest is being compared, and "N", "L" and "V" each represent different hypothetical nucleotides. Unless specifically stated otherwise, all % nucleic acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the AIIGN-2 computer program. 15 In other embodiments, TAT variant polynucleotides are nucleic acid molecules that encode a TAT polypeptide and which are capable of hybridizing, preferably under stringent hybridization and wash conditions, to nucleotide sequences encoding a full-length TAT polypeptide as disclosed herein. TAT variant polypeptides may be those that are encoded by a TAT variant polynucleotide. The term "full-length coding region" when used in reference to a nucleic acid encoding a TAT 20 polypeptide refers to the sequence of nucleotides which encode the full-length TAT polypeptide of the invention (which is often shown between start and stop codons, inclusive thereof, in the accompanying figures). The term "full-length coding region" when used in reference to an ATCC deposited nucleic acid refers to the TAT polypeptide-encoding portion of the cDNA that is inserted into the vector deposited with the ATCC (which is often shown between start and stop codons, inclusive thereof in the accompanying figures). ^25 "Isolated," when used to describe the various TAT polypeptides disclosed herein, means polypeptide that has been identified and separated and/or recovered from a component of its natural environment Contaminant components of its natural environment are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the polypeptide will be purified (1) to a degree sufficient to 30 obtain at least IS residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassieblue or, preferably, silver stain. Isolated polypeptide includes polypeptide in situ within recombinant cells, since at least one component of the TAT polypeptide natural environment will not be present Ordinarily, however, isolated polypeptide will be prepared by at least one purification step. 35 An "isolated" TAT polypeptide-encoding nucleic acid or other polypeptide-encoding nucleic acid is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecule with which it is ordinarily associated in the natural source of the polypeptide-encoding nucleic acid. An isolated 31 polypeptide-encoding nucleic acid molecule is other than in the form or setting in which it is found in nature. Isolated polypeptide-encoding nucleic acid molecules therefore are distinguished from the specific polypeptide-encoding nucleic acid molecule as it exists in natural cells. However, an isolated polypeptide-encoding nucleic acid molecule includes polypeptide-encoding nucleic acid molecules contained in cells that ordinarily express the polypeptide where, for example, the nucleic acid molecule is in a chromosomal location different from that of natural cells. The term "control sequences" refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are suitable forprokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaiyotic cells are known to utilize promoters, polyadenylation signals, and enhancers. Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, "operably linked" means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Unking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. "Stringency" of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature which can be used. As a result it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology. Wiley Interscience Publishers, (1995). "Stringent conditions" or "high stringency conditions", as defined herein, may be identified by those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50°C; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42°C; or (3) overnight hybridization in a solution that employs 50% formamide, 5 x SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5 xDenhardt's solution, sonicated salmon sperm DNA (50 ng/ml), 0.1% SDS, and 10% dextran sulfate at 42°C, with a 10 minute wash at 42°C in 0.2 x SSC (sodium chloride/sodium citrate) followed by a 10 minute high-stringency wash consisting of 0.1 x SSC containing EDTA at 55 °C. 32 "Moderately stringent conditions" may be identified as described by Sambrook et aL, Molecular Cloning- hybridization conditions (e.g., temperature, ionic strength and %SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37°C in a solution comprising: 20% formamide, 5 x SSC (150 mM NaCl, 15 mMtrisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 xDenhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-50°C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessaiy to accommodate factors such as probe length andthe like. - The term "epitope tagged" when used herein refers to a chimeric polypeptide comprising a TAT polypeptide or anti-TAT antibody fused to a "tag polypeptide". The tag polypeptide has enough residues to provide an epitope against which an antibody can be made, yet is short enough such that it does not interfere with activity of the polypeptide to which it is fused. The tag polypeptide preferably also is faiiiy unique so that the antibody does not substantially cross-react with other epitopes. Suitable tag polypeptides generally have at least six amino acid residues and usually between about 8 and 50 amino acid residues (preferably, between about 10 and 20 amino acid residues). "Active" or "activity" for the purposes herein refers to form(s) of a TAT polypeptide which retain a biological and/or an immunological activity of native or naturally-occurring TAT, wherein "biological" activity refers to a biological function (either inhibitory or stimulatory) caused by a native or naturally-occurring TAT other than the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring TAT and an "immunological" activity refers to the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring TAT. The term "antagonist" is used in the broadest sense, and includes any molecule that partially or fully blocks, inhibits, or neutralizes a biological activity of a native TAT polypeptide disclosed herein. In a similar manner, the term "agonist" is used in the broadest sense and includes any molecule that mimics a biological activity of a native TAT polypeptide disclosed herein. Suitable agonist or antagonist molecules specifically include agonist or antagonist antibodies or antibody fragments, fragments or amino acid sequence variants of native TAT polypeptides, peptides, antisense oligonucleotides, small organic molecules, etc. Methods for identifying agonists or antagonists of a TAT polypeptide may comprise contacting a TAT polypeptide with a candidate agonist or antagonist molecule and measuring a detectable change in one or more biological activities normally associated with the TAT polypeptide. "Treating" or "treatment" or "alleviation" refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented. A subject or mammal is successfully "treated" for a TAT polypeptide-expressing cancer if, after receiving a therapeutic amount of an anti-TAT antibody, TAT binding oligopeptide or TAT binding oiganic molecule according to the methods of the present invention, the patient shows observable and/or measurable reduction in or absence of one or more of the following: reduction in the number of cancer cells or absence of the cancer cells; reduction in the tumor size; inhibition (i.e., slow to some Cold Spring Harbor Press, 1989, and include the use of washing solution and 33 tissue and bone; inhibition (i.e., slow to some extent and preferably stop) of tumor metastasis; inhibition, to some extent, of tumor growth; and/or relief to some extent, one or more of the symptoms associated with the specific cancer; reduced morbidity and mortality, and improvement in quality of life issues. To the extent the anti-TAT antibody or TAT binding oligopeptide may prevent growth and/or kill existing cancer cells, it may be cytostatic 5 and/or cytotoxic. Reduction of these signs or symptoms may also be felt by the patient i The above parameters for assessing successful treatment and improvement in the disease are readily measurable by routine procedures familiar to a physician. For cancer therapy, efficacy can be measured,- for example, by assessing the time to disease progression (TIP) and/or determining the response rate (RR). Metastasis can be determined by staging tests and by bone scan and tests for calcium level and other enzymes 10 to determine spread to the bone. CT scans can also be done to look for spread to the pelvis and lymph nodes in the area. Chest X-rays and measurement of liver enzyme levels by known methods are used to look for metastasis to the lungs and liver, respectively. Other routine methods for monitoring the disease include transrectal ultrasonography(TRUS) and transrectal needle biopsy (TRNB). For bladder cancer, which is a more localized cancer, methods to determine progress of disease include 15 urinary cytologic evaluation by cystoscopy, monitoring for presence of blood in the urine, visualization of the urothelial tract by sonography or an intravenous pyelogram, computed tomography (CT) and magnetic resonance imaging (MRI). The presence of distant metastases can be assessed by CT of the abdomen, chest x-rays, or radionuclide imaging of die skeleton. "Chronic" administration refers to administration of die agent(s) in a continuous mode as opposed to an 20 acute mode, so as to maintain the initial therapeutic effect (activity) for an extended period of time. "Intermittent" administration is treatment that is not consecutively done without interruption, but rather is cyclic in nature. "Mammal" for purposes of the treatment of, alleviating the symptoms of or diagnosis of a cancer refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, cats, catde, horses, sheep, pigs, goats, rabbits, etc. Preferably, the mammal is human. 25 Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) and consecutive administration in any order. "Carriers" as used herein include pharmaceutical^ acceptable carriers, excipients, or stabilizers which are nontoxic to the cell or mammal being exposed thereto at die dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution. Examples of physiologically acceptable 30 carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol;' salt-forming 35 counterions such as sodium; and/or nonionic surfactants such as TWEEN®, polyethylene glycol (PEG), and PLURONICS®. 34 By "solid phase" or "solid support" is meant a non-aqueous matrix to which an antibody, TAT binding oligopeptide or TAT binding organic molecule of the present invention can adhere or attach. Examples of solid phases encompassed herein include those formed partially or entirely of glass (e.g., controlled pore glass), polysaccharides (e.g., agarose), polyacrylamides, polystyrene, polyvinyl alcohol and silicones. In certain embodiments, depending on the context, the solid phase can comprise the well of an assay plate; in others it is a purification column (e.g., an affinity chromatography column). This term also includes a discontinuous solid phase of discrete particles, such as those described in U.S. Patent No. 4,275,149. A "liposome" is a small vesicle composed of various types of lipids, phospholipids and/or surfactant which is useful for delivery of a drug (such as a TAT polypeptide, an antibody thereto or a TAT binding oligopeptide) to a mammal. The components of the liposome are commonly arranged in a bilayer formation, similar to the lipid arrangement of biological membranes. A"smalT molecule or "small" organic molecule is defined herein to have a molecular weight below about 500 Daltons. An "effective amount" of a polypeptide, antibody, TAT binding oligopeptide, TAT binding oiganic molecule or an agonist or antagonist thereof as disclosed herein is an amount sufficient to cany out a specifically stated purpose. An "effective amount" may be determined empirically and in a routine manner, in relation to the stated purpose. The term "therapeutically effective amount" refers to an amount of an antibody, polypeptide, TAT binding oligopeptide, TAT binding oiganic molecule or other drug effective to "treat" a disease or disorder in a subject or mammal la die case of cancer, the therapeutically effective amount of the drug may reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to some extent and preferably stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; inhibit, to some extent, tumor growth; and/or relieve to some extent one or more of the symptoms associated with the cancer. See the definition herein of "treating". To the extent the drug may prevent growth and/or kill existing cancer cells, it may be cytostatic and/or cytotoxic. A "growth inhibitoiy amount" of an anti-TAT antibody, TAT polypeptide, TAT binding oligopeptide or TAT binding organic molecule is an amount capable of inhibiting the growth of a cell, especially tumor, e.g., cancer cell, either in vitro or in vivo. A "growth inhibitoiy amount" of an anti-TAT antibody, TAT polypeptide, TAT binding oligopeptide or TAT binding organic molecule for purposes of inhibiting neoplastic cell growth may be determined empirically and in a routine manner. A "cytotoxic amount" of an anti-TAT antibody, TAT polypeptide, TAT binding oligopeptide or TAT binding organic molecule is an amount capable of causing the destruction of a cell, especially tumor, e.g., cancer cell, either in vitro or in vivo. A "cytotoxic amount" of an anti-TAT antibody, TAT polypeptide, TAT binding oligopeptide or TAT binding organic molecule for puiposes of inhibiting neoplastic cell growth may be determined empirically and in a routine manner. The term "antibody" is used in the broadest sense and specifically covers, for example, single anti-TAT monoclonal antibodies (Including agonist, antagonist, and neutralizing antibodies), anti-TAT antibody compositions with polyepitopic specificity, polyclonal antibodies, single chain anti-TAT antibodies, and fragments 35 of anti-TAT antibodies (see below) as long as they exhibit the desired biological or immunological activity. The term "immunoglobulin" (Ig) is used interchangeable with antibody herein. An "isolated antibody" is one which has been identified and separated and/or recovered from a component of its natural environment Contaminant components of its natural environment are materials which would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and 5 other proteinaceous or nonproteinaceous solutes. In preferred embodiments, the antibody will be purified (1) to greater than 95% by weight of antibody as determined by the Lowiy method, and most preferably more than 99% ' by weight, (2) to a degree sufficient to obtain at least 15 residues ofN-terminalorinternal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within 10 recombinant cells since at least one component of the antibody's natural environment will not be present Ordinarily, however, isolated antibody will be prepared by at least one purification step. The basic 4-chain antibody unit is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains (an IgM antibody consists of 5 of the basic heterotetramer unit along with an additional polypeptide called J chain, and therefore contain 10 antigen binding sites, while secreted IgA 15 antibodies can polymerize to form polyvalent assemblages comprising 2-5 of the basic 4-chain units along with Jcbain). In the case of IgGs, the 4-chain unit is generally about 150,000 daltons. Each L chain is linked to a H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype. Each H and L chain also has regularly spaced intrachain disulfide bridges. Each H chain has at the N-teiminus, a variable domain (V„) followed by three constant domains (Cg) for 20 each of the a and y chains and four C,, domains for |i and s isotypes. Each L chain has at the N-tenninus, a variable domain (VJ followed by a constant domain (Cy at its other end. The VL is aligned with the VH and the <\ is aligned with the first constant domain of the heavy chain (0,1). Particular amino acid residues are believed to form an interface between the light chain and heavy chain variable domains. The pairing of a VH and VL together forms a single antigen-binding site. For the structure and properties of the different classes of antibodies, see, e.g., Basic 25 and Clinical Immunology. 8th edition, Daniel P. Stites, Abba I. Terr and Tristram G. Parslow (eds.), Appleton & Lange, Norwalk, CT, 1994, page 71 and Chapter 6. The L chain from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains (Ch), immunoglobulins can be assigned to different classes 30 or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, having heavy chains designated a, 8, e, y, and n, respectively. The y and a classes are further divided into subclasses on the basis of relatively minor differences in CH sequence and function, e.g., humans express the following subclasses: IgGl, IgG2, IgG3, IgG4, IgAl, andIgA2. The term "variable" refers to the feet that certain segments of the variable domains differ extensively in 35 sequence among antibodies. The V domain mediates antigen binding and define specificity of a particular antibody for its particular antigen. However, the variability is not evenly distributed across the 110-amino acid span of the variable domains. Instead, the V regions consist of relatively invariant stretches called framework 36 regions (FRs) of 15-30 amino acids separated by shorter regions of extreme variability called "hypervariable regions" that are each 9-12 amino acids long. The variable domains of native heavy and light chains each comprise four FRs, largely adopting a 0-sheet configuration, connected by three hypervariable regions, which form loops connecting, and in some cases forming part of, the p-sheet structure. The hypervariable regions in each chain are held together in close proximity by the FRs and, with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Rabat et aL, Sequences of Proteins <*fTtrnnnnnlopinnl Interest 5thEd. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). The constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of Ihe antibody in antibody dependent cellular cytotoxicity (ADCC). The term "hypervariable region" when used herein refers to the amino acid residues of an antibody which axe responsible for antigen-binding. The hypervariable region generally comprises amino acid residues from a "complementarity determining region" or"CDR" (e.g. around about residues 24-34 (LI), 50-56 (L2) and 89-97 (L3) inthe Vu and around about 1-35 (HI), 50-65 (H2) and 95-102 (H3) in the VH; Kabat et al., Sequences of Proteins of Immunological Interest 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)) and/or those residues from a "hypervariable loop" (e.g. residues 26-32 (LI), 50-52 (L2) and 91-96 (L3) inthe and 26-32 CHI), 53-55 (H2) and 96-101 (H3) in the VH; Chothia andLesk J.Mol.Biol. 196:901-917 (1987)). The term "monoclonal antibody" as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising Ihe population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to polyclonal antibody preparations which include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. la addition to their specificity, the monoclonal antibodies are advantageous in that they may be synthesized uncontaminated by other antibodies. The modifier "monoclonal" is not to be construed as requiring production of tilie antibody by any particular method. For example, the monoclonal antibodies useful in the present invention may be prepared by the hybridoma methodology first described by Kohler et aL, Nature. 256:495 (1975), or may be made using recombinant DNA methods in bacterial, eukaiyotic animal or plant cells (see, e.g., U.S. Patent No. 4,816,567). The "monoclonal antibodies" may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature. 352:624-628 (1991) and Marks et al., J. Mol. Biol.. 222:581-597 (1991), for example. The monoclonal antibodies herein include "chimeric" antibodies in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see U.S. Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA. 81:6851-6855 (1984)). Chimeric antibodies of interest herein include "primatized" antibodies comprising variable domain antigen-binding sequences derived from a non-human primate (e.g. Old World Monkey, Ape etc), and human constant region sequences. 37 An "intact" antibody is one which comprises an antigen-binding site as well as a Q, and at least heavy chain constant domains, CH1, CH2 and C„3. The constant domains may be native sequence constant domains (e.g. human native sequence constant domains) or amino acid sequence variant thereof. Preferably, the intact antibody has one or more effector Amotions. "Antibody fragments" comprise a portion of an intact antibody, preferably the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies (see U.S. PatentNo. 5,641,870, Example 2; Zapata et al.. Protein Eng. SflO: 1057-1062 [1995]); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produces two identical antigen-binding fragments, called 'Tab" fragments, and a residual "Fc" fragment, a designation reflecting the ability to crystallize readily. The Fab fragment consists of an entire L chain along with the variable region domain of the H chain (Vg), and the first constant domain of one heavy chain (CH1). Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab')j fragment which roughly corresponds to two disulfide linked Fab fragments having divalent antigen-binding activity and is still capable of cross-linking antigen. Fab' fragments differ from Fab fragments by having additional few residues at the caiboxy terminus of theCj,l domain including one or more cysteines from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab*)2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known. The Fc fragment comprises the carboxy-terminal portions of both H chains held together by disulfides. The effector functions of antibodies are determined by sequences in the Fc region, which region is also the part recognized by Fc receptors (FcR) found on certain types of cells. "Fv" is the minimum antibody fragment which contains a complete antigen-recognition and -binding site. This fragment consists of a dimer of one heavy- and one light-chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (3 loops each from the H and L chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of anFv comprising only three CDRs specific for an qntigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site. "Single-chain Fv" also abbreviated as "sFv" or "scFv" are antibody fragments that comprise the VH and VL antibody domains connected into a single polypeptide chain. Preferably, the sFv polypeptide further comprises a polypeptide linker between the VK and Vt domains which enables the sFv to form the desired structure for antigen binding. For a review of sFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994); Boirebaeck 1995, infra. The term "diabodies" refers to small antibody fragments prepared by constructing sFv fragments (see preceding paragraph) with short linkers (about 5-10 residues) between the VH and VL domains such that inter-chain but not intra-chain pairing of the V domains is achieved, resulting in a bivalent fragment, Le., fragment having two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" sFv fragments in which the VH and VL domains of the two antibodies are present on different polypeptide chains. Diabodies are described more 38 fully in, for example, EP404,097; WO 93/11161; andHolIinger et al., Proc. Natl. Acad. ScL USA, 90:6444-6448 (1993). "Humanized" forms of non-human (e.g., rodent) antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody. For die most part, humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a hypervariable region of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or 5 non-human primate having the desired antibody specificity, affinity, and capability. In some instances, framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or 10 substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FRs are those of a human immunoglobulin sequence. The humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al.. Nature 321:522-525 (1986): Riechmann et al.. Nature332:323-329 (1988); and Presta, Curr. Oo. Struct BioL 2:593-596 (1992). IS A "species-dependent antibody," e.g., a mammalian anti-human IgE antibody, is an antibody which has a stronger binding affinity for an antigen from a first mammalian species than it has for a homologue of that antigen from a second mammalian species. Normally, the species-dependent antibody "bind specifically" to a human antigen (i.e., has a binding affinity (Kd) value of no more than about 1 x 10"7 M, preferably no more than about 1 x 10"8 and most preferably no more than about 1 x 10"9M) but has a binding affinity for a homologue of the antigen 20 from a second non-human mammalian species which is at least about 50 fold, or at least about 500 fold, or at least about 1000 fold, weaker than its binding affinity for the human antigen. The species-dependent antibody can be of any of the various types of antibodies as defined above, but preferably is a humanized or human antibody. A "TAT binding oligopeptide" is an oligopeptide that binds, preferably specifically, to a TAT polypeptide as described herein. TAT binding oligopeptides may be chemically synthesized using known 25 oligopeptide synthesis methodology or may be prepared and purified using recombinant technology. TAT binding oligopeptides are usually at least about 5 amino acids in length, alternatively at least about 6,7,8,9,10, 11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43, 44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76, 77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99, or 100 amino acids in length ormore, 30 wherein such oligopeptides that are capable of binding, preferably specifically, to a TAT polypeptide as described herein. TAT binding oligopeptides may be identified without undue experimentation using well known techniques. In this regard, it is noted that techniques for screening oligopeptide libraries for oligopeptides that are capable of specifically binding toapolypeptide target are well known in the art(see,e.g.,U.S.PatentNos. 5,556,762,5,750,373, 4,708,871,4,833,092,5,223,409,5,403,484,5,571,689,5,663,143; PCT PublicationNos. WO84/03506and W084/03564; 35 Geysen et al., Proc. Natl. Acad. Sci. U.S.A., 81:3998-4002 (1984); Geysen et al., Proc. Natl. Acad. Sci. U.SA., 82:178-182 (1985); Geysen et al., in Synthetic Peptides as Antigens, 130-149 (1986); Geysen etal., J. Immunol. Meth., 102:259-274(1987); Schoofs etal., J. Immunol., 140:611-616 (1988), Cwtria, S.E. etal. (1990) Proc. Natl. Acad. Sci. 39 USA, 87:6378; Lowman, HJB. et al. (1991) Biochemistry,30:10832; Clackson, T. et al. (1991) Nature,352:624; Maries, I. D. etal. (1991), X. Mol. Biol., 222:581; Kaog, A.S. etal. (1991) Proc. Natl. Acad. Sci. USA, 88:8363, and Smith, O. P. (1991) Current Opin. Biotechnol., 2:668). A 'TAT binding organic molecule" is an organic molecule other than an oligopeptide or antibody as defined herein that binds, preferably specifically, to a TAT polypeptide as described herein. TAT binding organic molecules maybe identified and chemically synthesized using knownmethodology (see, e.g., PCT PublicationNos. W000/00823 and WOOO/39585). TAT binding organic molecules are usually less than about 2000 daltons in size, alternatively less than about 1500,750; 500,250 or 200 daltons in size, wherein such organic molecules that are capable of binding, preferably specifically, to a TAT polypqptide as described herein may be identified without undue experimentation using well known techniques. In this regard, it is noted that techniques for screening organic molecule libraries for molecules that are capable of binding to a polypqptide target are well known in the art (see, e.g., PCT PublicationNos. W000/00823 and WOOO/39585). An antibody, oligopeptide or other organic molecule "which binds" an antigen of interest, e.g. a tumor-associated polypqptide antigen target, is one that'binds the antigen with sufficient affinity such that the antibody, oligopeptide or other organic molecule is useful as a diagnostic and/or therapeutic agent in targeting a cell or tissue expressing the antigen, and does not significantly cross-react with other proteins. In such embodiments, the extent of binding of the antibody, oligopeptide or other organic molecule to a "non-target" protein will be less than about 10% of the binding of the antibody, oligopeptide or other organic molecule to its particular target protein as determined by fluorescence activated cell sorting (FACS) analysis or radioimmunoprecipitation (RIA). With regard to die binding of an antibody, oligopeptide or other organic molecule to a target molecule, the term "specific binding" or "specifically binds to" or is "specific for" a particular polypeptide or an epitope on a particular polypeptide target means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by detennining binding of a molecule compared to binding of a control molecule, which generally is a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target for example, an excess of non-labeled target In tins case, specific binding is indicated if the binding of the labeled target to a probe is competitively inhibited by excess unlabeled target The term "specific binding" or "specifically binds to" or is "specific for" a particular polypeptide or an epitope on a particular polypeptide target as used herein can be exhibited, for example, by a molecule having a Kd for the target of at least about 10"4 M, alternatively at least about 10"SM, alternatively at least about 10"6 M, alternatively at least about 10"7 M, alternatively at least about 10"8 M, alternatively at least about 10"9 M, alternatively at least about 10"10 M, alternatively at least about 10"u M, alternatively at least about 10"12 M, or greater. In one embodiment, the term "specific binding" refers to binding where a molecule binds to a particular polypeptide or epitope on a particular polypqptide without substantially binding to any other polypeptide or polypeptide epitope. An antibody, oligopeptide or other organic molecule that "inhibits the growth of tumor cells expressing a TAT polypeptide" or a "growth inhibitory" antibody, oligopeptide or other organic molecule is one which results in measurable growth inhibition of cancer cells expressing or overexpressing the appropriate TAT polypeptide. The TAT polypeptide may be a transmembrane polypqptide expressed on the surface of a cancer cell or may be 40 a polypqptide that is produced and secreted by a cancer cell. Preferred growth inhibitory anti-TAT antibodies, oligopeptides or oiganic molecules inhibit growth of TAT-expressing tumor cells by greater than 20%, preferably from about 20% to about 50%, and even more preferably, by greater than 50% (e.g., from about 50% to about 100%) as compared to the appropriate control, the control typically being tumor cells not treated with the antibody, oligopeptide or other organic molecule being tested. In one embodiment, growth inhibition can be measured at an antibody concentration of about 0.1 to 30 |ig/ml or about 0.5 nM to 200 nM in cell culture, where the growth inhibition is determined 1-10 days after exposure of the tumor cells to the antibody. Growfli inhibition of tumor cells in vivo can be determined in various ways such as is described in the Experimental Examples section below.-The antibody is growth inhibitoiy in vivo if administration of the anti-TAT antibody at about 1 jig/kg to about 100 mg/kg body weight results in reduction in tumor size or tumor cell proliferation within about 5 days to 3 months from the first administration of the antibody, preferably within about 5 to 30 days. An antibody, oligopeptide or other oiganic molecule which "induces apoptosis" is one which induces programmed cell death as detennined by binding of annexin V, fragmentation of DNA, cell shrinkage, dilation of endoplasmic reticulum, cell fragmentation, and/or formation of membrane vesicles (called apoptotic bodies). The cell is usually one which overexpresses a TAT polypeptide. Preferably the cell is a tumor cell, e.g., a prostate, breast, ovarian, stomach, endometrial, lung, kidney, colon, bladder cell. Various methods are available for evaluating the cellular events associated with apoptosis. For example, phosphatidyl serine (PS) translocation can be measured by annexin binding; DNA fragmentation cm be evaluated through DNA laddering; and nuclear/chromatin condensation along with DNA fragmentation can be evaluated by any increase in hypodiploid cells. Preferably, the antibody, oligopeptide or other organic molecule which induces apoptosis is one which results in about 2 to 50 fold, preferably about 5 to 50 fold, and most preferably about 10 to 50 fold, induction of annexin binding relative to untreated cell in an annexin binding assay. Antibody "effector functions" refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vaiy with the antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation. "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" refers to a form of cytotoxicity in which secreted Ig bound onto Fc receptors (FcRs) present on certain cytotoxic cells (e.g., Natural Killer (NK) cells, neutrophils, and macrophages) enable these cytotoxic effector cells to bind specifically to an antigen-bearing target cell and subsequently kill the target cell with cytotoxins. The antibodies "aim" the cytotoxic cells and are absolutely required for suchkilling. The primary cells for mediating ADCC, NK cells, express FcyRBOt only, whereas monocytes express FcyRI, FcyRII and FcyRHI. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch andKinet, Annu. Rev. Immunol. 9:457-92 (1991). To assess ADCC activity of a molecule of interest, an in vitro ADCC assay, such as that described inUS PatentNo. 5,500,362 or 5,821,337 may be performed. UseM effector cells for such assays include peripheral blood mononuclear cells (PBMQ and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in a animal model such as that disclosed in Clynes et al. (USA) 95:652-656 (1998). 41 "Fc receptor" or "FcR" describes a receptor that binds to the Fc region of an antibody. The preferred FcR is a native sequence human FcR. Moreover, a preferred FcR is one which binds an IgG antibody (a gamma receptor) and includes receptors of the FcyRI, FcyRQ and FcyRin subclasses, including allelic variants and alternatively spliced forms of these receptors. FcyRH receptors include FcyRIIA (an "activating receptor") and FcyBUB (an "inhibiting receptor"), which have similar amino acid sequences that differ primarily in the cytoplasmic domains thereof. Activating receptor FcyRIIA contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. Inhibiting receptor FcyRUB contains an immunoreceptor tyrosine-based inhibition motif(nTM) in its cytoplasmic domain: (see review M. in DaSron, Annu. Rev. Immunol. 15:203-234 (1997)). FcRs are reviewed in Ravetch and Kinet, Annu. Rev. Immunol. 9:457-492 (1991); Capel et al., Imnfiunomethods4:25-34 ("1994'): and deHaas etal.. J. Lab. Clin. Med. 126:330-41 (1995). Other FcRs, including those to be identified in the future, are encompassed by the term "FcR" herein. The term also includes the neonatal receptor, FcRn, which is responsible for the transfer of maternal IgGs to the fetus (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., -T. Immunol. 24:249 (1994)). "Human effector cells" are leukocytes which express one or more FcRs and perform effector functions. Preferably, the cells express at least FcyRIH and perform ADCC effector function. Examples of human leukocytes which mediate ADCC include peripheral blood mononuclear cells (PBMC), natural killer (NK) cells, monocytes, cytotoxic T cells and neutrophils; with PBMCs and NK cells being preferred. The effector cells may be isolated from a native source, e.g., from blood. "Complement dependent cytotoxicity" or "CDC" refers to the lysis of a target cell in the presence of complement Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (Clq) to antibodies (of the appropriate subclass) which are bound to their cognate antigen. To assess complement activation, a CDC assay, e.g., as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996), may be performed. The terms "cancer" and "cancerous" refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastema, sarcoma, and leukemia or lymphoid malignancies. More particular examples of such cancers include squamous cell cancer (e.g., epithelial squamous cell cancer), lung cancer including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung and squamous carcinoma of Ihe lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, cancer of the urinary tract, hepatoma, breast cancer, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, melanoma, multiple myeloma and B-cell lymphoma, brain, as well as head and neck cancer, and associated metastases. The terms "cell proliferative disorder" and "proliferative disorder" refer to disorders that are associated with some degree of abnormal cell proliferation. In one embodiment, the cell proliferative disorder is cancer. "Tumor", as used herein, refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. 42 An antibody, oligopeptide or other organic molecule which "induces cell death" is one which causes a viable cell to become nonviable. The cell is one which expresses a TAT polypeptide, preferably a cell that overexpresses a TAT polypeptide as compared to a normal cell of the same tissue type. The TAT polypeptide may be a transmembrane polypeptide expressed on the surface of a cancer cell or may be a polypeptide that is produced and secreted by a cancer cell. Preferably, the cell is a cancer cell, e.g., a breast, ovarian, stomach, endometrial, salivary gland, lung, kidney, colon, thyroid, pancreatic or bladder cell. Cell death in vitro may be determined in the absence of complement and immune effector cells to distinguish cell death induced by antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (GDC). Thus, die assay for cell death may be performed using heat inactivated serum (i.e., in the absence of complement) and in the absence of immune effector cells. To determine whether the antibody, oligopeptide or other organic molecule is able to induce cell death, loss of membrane integrity as evaluated by uptake of propidium iodide (PI), trypan blue (see Moore et al. Cvtotechnologv 17:1-11 (1995)) or 7AAD can be assessed relative to untreated cells. Preferred cell death-inducing antibodies, oligopeptides or other organic molecules are those which induce PI uptake in the PI uptake assay in BT474 cells. A "TAT-expressing cell" is a cell which expresses an endogenous or transfected TAJ polypeptide either on the cell surfece or in a secreted form. A 'TAT-expressing cancer" is a cancer comprising cells that have a TAT polypeptide present on the cell surfece or that produce and secrete a TAT polypqptide. A 'TAT-expressing cancer" optionally produces sufficient levels of TAT polypeptide on the surfece of cells thereof, such that an anti-TAT antibody, oligopeptide ot other oiganic molecule can bind thereto and have a therapeutic effect with respect to the cancer. In another embodiment, a TAT-expressing cancer" optionally produces and secretes sufficient levels of TAT polypqptide, such that an anti-TAT antibody, oligopeptide ot other organic molecule antagonist can bind thereto and have a therapeutic effect with respect to the cancer. With regard to the latter, the antagonist may be an antisense oligonucleotide which reduces, inhibits or prevents production and secretion of the secreted TAT polypeptide by tumor cells. A cancer which "overexpresses" a TAT polypeptide is one which has significantly higher levels of TAT polypeptide at the cell surfece thereof, or produces and secretes, compared to a noncancerous cell of the same tissue type. Such overexpression may be caused by gene amplification or by increased transcription or translation. TAT polypeptide overexpression may be determined in a diagnostic or prognostic assay by evaluating increased levels of the TAT protein present on the surfece of a cell, or secreted by the cell (e.g., via an immunohistochemistry assay using anti-TAT antibodies prepared against an isolated TAT polypeptide which may be prepared using recombinant DNA technology from an isolated nucleic acid encoding the TAT polypeptide; FACS analysis, etc.). Alternatively, or additionally, one may measure levels of TAT polypeptide-encoding nucleic acid or mBNA in the cell, e.g., via fluorescent in situ hybridization using a nucleic acid based probe corresponding to a TAT-encoding nucleic acid or the complement thereof; (FISH; see • W098/45479 published October, 1998), Southern blotting, Northern blotting, or polymerase chain reaction (PCR) techniques, such as real time quantitative PCR (RT-PCR). One may also study TAT polypqptide overexpression by measuring shed antigen in a biological fluid such as serum, e.g, using antibody-based assays (see also, e.g., U.S.PatentNo.4,933,294 issued June 12,1990; W091/05264published April 18,1991; U.S.Patent5,401,638 issued March 28,1995; and Sias et al., I. Immunol. Methods 132:73-80 (1990)). Aside from the above assays, various in 43 vivo assays ace available to the skilled practitioner. For example, one may expose cells within the body of the patient to an antibody which is optionally labeled with a detectable label, e.g., a radioactive isotope, and binding of the antibody to cells in the patient can be evaluated, e.g., by external scanning for radioactivity or by analyzing a biopsy taken from a patient previously exposed to Ihe antibody. As used herein, the term "immunoadhesin" designates antibody-like molecules which combine the binding specificity of a heterologous protein (an "adhesin") with the effector functions of immunoglobulin constant domains. Structurally, flue immunoadhesins comprise a fusion of an amino acid sequence with the desired binding specificity which is other than the antigen recognition and binding site of an antibody (ie., is "heterologous"), and an immunoglobulin constant domain sequence. The adhesin part of an immunoadhesin molecule typically is a contiguous amino acid sequence comprising at least the binding site of a receptor or a ligand. The immunoglobulin constant domain sequence in the immunoadhesin may be obtained from any immunoglobulin, such as IgG-1, IgG-2, IgG-3, or IgO-4 subtypes, IgA (including IgA-1 and IgA-2), IgE, IgD or IgM. The word "label" when used herein refers to a detectable compound or composition which is conjugated directly or indirectly to the antibody, oligopeptide or other organic molecule so as to generate a "labeled" antibody, oligopeptide or other organic molecule. The label may be detectable by itself (e.g. radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition which is detectable. The term "cytotoxic agent" as used herein refers to a substance that inhibits or prevents the function of cells and/or causes destruction of cells. The term is intended to include radioactive isotopes (e.g., At211,1131,1125, Y90, Re186, Re188, Sm153, Bi212, P32 and radioactive isotopes of Lu), chemotherapeutic agents e.g. methotrexate, adriamicin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, dauHorubicin or other intercalating agents, enzymes and fragments thereof such as nucleolytic enzymes, antibiotics, and toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and/or variants thereof, and the various antitumor or anticancer agents disclosed below. Other cytotoxic agents are described below. A tumoricidal agent causes destruction of tumor cells. A "growth inhibitoiy agent" when used herein refers to a compound or composition which inhibits growth of a cell, especially a TAT-expressing cancer cell, either in vitro or in vivo. Thus, the growtii inhibitory agent may be one which significantly reduces the percentage of TAT-expressing cells in S phase. Examples of growth inhibitory agents include agents that block cell cycle progression (at a place other than S phase), such as agents that induce G1 arrest and M-phase arrest Classical M-phase blockers include the vincas (vincristine and vinblastine), taxanes, and topoisomerase II inhibitors such as doxorubicin, epirubicin, daunorubicin, etoposide, and bleomycin. Those agents that arrest 01 also spill over into S-phase arrest, for example, DNA alkylating agents such as tamoxifen, prednisone, dacarbazine, mechlorethamine, cisplatin, methotrexate, 5-fluorouracil, and ara-C. Further information can be found in The Molecular Basis of Cancer. Mendelsohn and Israel, eds,, Chapter 1, entitled "Cell cycle regulation, oncogenes, and antineoplastic drugs" by Murakami et al. (WB Saunders: Philadelphia, 1995), especially p. 13. The taxanes (paclitaxel and docetaxel) are anticancer drugs both derived from the yew tree. Docetaxel (TAXOTERE®, Rhone-Poulenc Rorer), derived from the European yew, is a semisynthetic 44 10 15 20 * 25 analogue of paclitaxel (TAXOL®, Bristol-Myers Squibb). Paclitaxel and docetaxel promote the assembly of microtubules from tubulin dimers and stabilize microtubules by preventing depolymerization, which results in the inhibition of mitosis in cells. "Doxorubicin" is an anthracycline antibiotic. The full chemical name of doxorubicin is (8S-cis)-10-[(3-anuno-2,3,6-trideoxy-a-L-lyxo-hexapyranosyl)oxy]-7,8,9,10-tetrabydro-6,8,ll-trihydxoxy-8-(hydroxyacetyl)-l-methoxy-5,12-naphthacenedione. The term "cytokine" is a generic term for proteins released by one cell population which act on another cell as intercellular mediators. Examples of such cytokines are lymphokines, monokines, and traditional polypeptide hormones. Included among the cytokines are growfli hormone such as human growth hormone, N-methionyl human growfli hormone, and bovine growth hormone; parathyroid hormone; thyroxine; insulin; proinsulin; relaxin; prorelaxin; glycoprotein hormones such as follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), and luteinizing hormone (LH); hepatic growth factor; fibroblast growth fector; prolactin; placental lactogen; tumor necrosis fector-a and -(}; muUerian-inhibiting substance; mouse gonadotropin-associated peptide; inhibin; activin; vascular endothelial growth factor, integrin; thrombopoietin (TPO); oerve growth factors such as NGF-P; platelet-growth fector, transforming growth factors (TGFs) such as TGF-a and TGF-P; insulin-like growth factor-I and -IE; erythropoietin (EPO); osteoinductive factors; interferons such as interferon -a, -p, and -y; colony stimulating factors (CSFs) such as macrophage-CSF (M-CSF); granulocyte-macrophage-CSF (GM-CSF); andgranulocyte-CSF (G-CSF); interleukins (ILs) such as IL-1, IL- la, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-11, IL-12; a tumor necrosis fector such as TNF-a or TNF-B; and other polypeptide factors including UF and kit ligand (KL). As used herein, the term cytokine includes proteins from natural sources or from recombinant cell culture and biologically active equivalents of the native sequence cytokines. The term "package insert" is used to refer to instructions customarily included in commercial packages of therapeutic products, that contain information about the indications, usage, dosage, administration, contraindications and/or warnings concerning the use of such therapeutic products. "Psoriasis" and/or a "psoriatic condition" is an inflammatory disease characterized by hyperproliferation of keratinocytes and accumulation of activated T cells in the epidermis and dermis of psoriatic lesions. Compositions of matter of the present invention may be used to treat psoriasis where therapeutic effect is determined by a physician's global assessment (PGA) of the patient and by Psoriases Area and Severity liidex (PAS1) scores. A decrease in PASI score indicates a therapeutic effect Psoriatic disease activity can also be determined based on Overall Lesion Severity (OLS) scale, percentage of total body surfece area (BSA) affected by psoriasis, and psoriasis plaque thickness. The term "comprising" as used in this specification means "consisting at least in part of". When interpreting each statement in this specification that includes the term "comprising", features other than that or those prefaced by the term may also be present. Related terms such as "comprise" and "comprises" are to be interpreted in the same manner. 45 Table 1 /♦ * * C-C increased from 12 to IS *Z is average of EQ 5 * Bis average of ND * match with stop is _M; stop-stop = 0; J (joker) match = 0 */ #deflne _M -8 /* value of a match with a stop*/ 10 - int _day[26][26]={ /* ABCDBFGHIJKLMNOPQRSTUVWXYZ*/ /* A*/ {2,0,-2,0,0,-4,1,-1,-1,0,-1,-2,-1,0,_M, 1,0,-2,1,1,0,0,-6,0,-3,0}, /* B */ {0,3,-4,3,2,-5,0,1,-2,0,0,-3,-2,2,_M,-1,1,0,0,0,0,-2,-5,0,-3,1}, /*C*/ {-2,-4,15,-5,-5,-4,-3,-3,-2,0,-5,-6,-5,-4,_M,-3,-5,-4,0,-2,0,-2,-8,0,0,-5}, 15 /* D */ {0,3,-5,4,3,-6,1,1,-2,0,0,-4,-3,2,_M,-1,2,-1,0,0,0,-2,-7,0,-4,2}, t*B*l { 0,2,-5,3,4,-5,0,1,-2,0,0,-3,-2,1,_M,-1,2,-1,0,0,0,-2,-7,0,-4,3}, /*¥*/ {-4,-5,-4,-6,-5,9,-5,-2,1,0,-5,2,0,-4,_M,-5,-5,-4,-3,-3,0,-1,0,0,7,-5}, /* G */ {1,0,-3,1,0,-5,5,-2,-3,0,-2,-4,-3,0,_M,-l,-l,-3,1,0,0,-1,-7,0,-5,0}, /* H */ (-1,1,-3,1,1,-2,-2,6,-2,0,0,-2,-2,2,_M, 0,3,2,-1,-1,0,-2,-3,0,0,2}, 20 1*1*1 {-1,-2,-2,-2,-2,1,-3,-2,5,0,-2,2,2,-2,_M,-2,-2,-2,-1,0,0,4,-5,0,-1,-2}, 1*1*1 { 0,0,0,0,0,0,0,0,0,0,0,0,0,0 JM, 0,0,0,0,0,0,0,0,0,0,0}, /* K */ {-1,0,-5,0,0,-5,-2,0,-2,0,5,-3,0,1,_M,-1,1,3,0,0,0,-2,-3,0,-4,0}, /* L*/ {-2,-3,-6,-4,-3,2,-4,-2,2,0,-3,6,4,-3,_M,-3,-2,-3,-3,-1,0,2,-2,0,-1,-2}, !* M *1 {-1,-2,-5,-3,-2,0,-3,-2,2,0,0,4,6,-2Jvt,-2,-l, 0,-2,-1,0,2,-4,0,-2,-1}, 25 /*N*/ {0,2,-4,2,1,-4,0,2,-2,0,1,-3,-2,2,_M,-1,1,0,1,0,0,-2,-4,0,-2,1}, /* O *1 0,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M}, /* P */ { 1,-1,-3,-1,-1,-5,-1,0,-2,0,-l,-3,-2,-l,_M, 6,0,0,1,0,0,-1,-6,0,-5,0}, I* Q */ {0,1,-5,2,2,-5,-1,3,-2,0,1 ,-2,-1,1,_M, 0,4,1,-1,-1,0,-2,-5,0,-4,3}, /*R*/ {-2,0,-4,-1,-1,-4,-3,2,-2,0,3,-3,0,0,_M, 0,1,6,0,-1,0,-2,2,0,-4,0}, 30 /*S*I {1,0,0,0,0,-3,1,-1,-1,0,0,-3,-2,1,_M> 1,-1,0,2,1,0,-1,-2,0,-3,0}, 1*1*1 {1,0,-2,0,0,-3,0,-1,0,0,0,-1,-1,0,_M, 0,-1,-1,1,3,0,0,-5,0,-3,0}, I* U *1 { 0,0,0,0,0,0,0,0,0,0,0,0,0,0,_M, 0,0,0,0,0,0,0,0,0,0,0}, /*V*/ { 0,-2,-2,-2,-2,-1,-1,-2,4,0,-2,2,2,-2,_M,-1,-2,-2,-1,0,0,4,-6,0,-2,-2}, /*WV {-6,-5,-8,-7,-7,0,-7,-3,-5,0,-3,-2,-4,-4^M,-6,-5,2,-2,-5,0,-6,17,0,0,-6}, 35 /*X*I {0,0,0,0,0,0,0,0,0,0,0,0,0,0,_M, 0,0,0,0,0,0,0,0,0,0,0}, /* Y */ {-3,-3,0,-4,-4,7,-5,0,-1,0,-4,-1 ,-2,-2,_M,-5,-4,-4,-3,-3,0,-2,0,0,10,-4}, )*Z*l {0,1,-5,2,3,-5,0,2,-2,0,0,-2,-1, ljtf,0,3,0,0,0,0,-2,-6,0,-4,4} I 40 45 50 46 Table 1 fcontn 10 15 20 /« */ #include <stdio.h> #include <ctype.h> #define MAXJMP 16 J* max jumps in a diag */ #define MAXOAP 24 /* don't continue to penalize gaps laiger than this */ #deflne JMPS 1024 /* max jmps in an path */ #deflne MX 4 /* save if there's at least MX-1 bases since last jmp */ #define 0MAT 3 1* value of matching bases */ #define DMIS 0 /* penalty for mismatched bases */ #define DINSO 8 t* penalty for a gap */ #deflne DINS1 1 /* penalty per base */ #deflne PINS0 8 I* penalty for a gap */ #define PINS1 4 /* penalty per residue */ struct jmp { short njMAXJMP]; unsigned short x[MAXJMP]; >; /* size of jmp (neg for dely) */ /* base no. of jmp in seq x */ /* limits seq to 2A16 -1 */ struct diag { tat 25 king short struct jmp }; 30 struct path { 35 40 45 50 score; offset; ijmp; jp; /* score at last jmp */ /* offset of prev block */ /* current jmp index */ /* listofjmps */ int spc; /* number of leading spaces */ short n[JMPS]; /* size of jmp (gap) */ }; int x[JMPS]; t* loc of jmp (last elan before gap) */ char *ofile; /* output file name */ char #namex[2]; /* seq names: getseqsO */ char ♦prog? J* prog name for err msgs */ char *seqx[2]; /* seqs: getseqsO */ int dmax; /* best diag: nwO *! int dmaxO; 1* final diag */ Int dna; /* set if dna: mainO */ int endgaps; /* set if penalizing aid gaps */ int gapx, gapy; /* total gaps in seqs */ int lenO.lenl; /* seq Iras*/ int ngapx, ngapy; /* total size of gaps */ int smax; /* max score: nwO */ int *xbm; /* bitmap for matching */ long offset; /* current offset in jmp file */ struct diag *dx; /* holds diagonals */ struct path pp[2]; /* holds path for seqs */ char ♦callocQ, *malloc0, *index(), *strcpyQ; char *getseq0> *g_ callocQ; 47 Table 1 (contn /* Needleman-Wunsch alignment program * * usage; progs filel file2 * where filel and file2 are two dna or two protein sequences. 5 41 The sequences can be in upper- or lower-case an may contain ambiguity * Any lines beginning withor '<■ are ignored * Max file length is 65535 (limited by unsigned short x in the jmp struct) * A sequence with 1/3 or more of its elements ACGTU is assumed to be DNA * Output is in the file "align.out" 10 * * The program may create a tap file in /tmp to hold info about traceback. * Original version developed under BSD 4.3 on a vax 8650 */ #include "nw.h" 15 #include "day.h" static _dbval[26] = { 1,14,2,13,0,0,4,11,0,0,12,0,3,15,0,0,0,5,6,8,8,7,9,0,10,0 }; 20 static _pbval[26] = { 1,2|(l«(rD'-,A,))|(l «CNI-'A')), 4,8,16,32,64, 128,256, OxFFFFFFF, 1«10,1«11,1«12,1«13,1«14, . 1«15,1«16,1<<17,1«18,1«19,1«20,1«21,1«22, 25 1«23,1«24, l«25|(l«CE'-'A'))|(l«('Q'-'A')) >; main(ac, av) maill int ac; 30 char *avQ; { prog=av[0]; if (ac != 3) { fprintf(stderr,"usage: %s filel file2\n", prog); 3 5 fprintf^stderr,"where filel and file2 are two dna or two protein sequencesAn"); %irint{(stderr,"The sequences can be in upper- or lower-case\n"); fprintf(stderr,"Any lines beginning withor '< are ignored\n"); fc fprintf(stderr,"Output is in the file \"align.out\"\n"); W exit(l); 40 } namex[0] = av[l]; namexfl] = av[2]; seqx[0] = getseq(namex[0], &len0); seqxfl] = getseq(namexfl], &lenl); 45 xbm = (dna)? .dbval: jjbval; endgaps = 0; /* 1 to penalize endgaps */ ofile = *align.out"; /* output file */ 50 nwO; /* fill in the matrix, get the possible jmps*/ reacfjmpsO; /* get the actual jmps */ printO; /* print stats, alignment */ oleanup(0); /* unlink any tmp files */} 48 5 10 15 20 25 30 35 40 45 50 55 Table 1 (cont^ /* do the alignment, return best score: mainO * dna: values in Fitch and Smith, PNAS, 80,1382-1386,1983 * pro: PAM 250 values * When scores are equal, we prefer mismatches to any gap, prefer * a new gap to extending an ongoing gap, and prefer a gap in seqx * to a gap in seq y. */ nwO nw { char *px> *py; /*seqs andptrs */ int *ndely, *dely; I* keep track of dely */ int ndelx, delx; /* keep track of delx */ Int "■tap; /* for swsqpping rowO, rowl */ int mis; /* score for each type */ int insO, insl; /* insertion penalties *1 register id; /* diagonal index */ register ij; /♦jmp index*/ register *colO, *coll;- /* score for curr, last row */ register xx, yy; /* index into seqs*/ dx = (struct diig *)g_calloc("to get diags", lenO+lenl+l, sizeof(struct diag)); ndely = (tat *)g_calloc("to get ndely", lenl+1, sizeof(Int)); dely — (Int *)g_calloc("to get dely", lenl+1, sizeof(int)); colO = (int *)g_calloc("to get colO", lenl+1, sizeof(hit)); coll = (tat *)g_calloc("to get coll", lenl+1, sizeof(int)); insO >= (dna)? DINSO: PINSO; insl = (dna)? DINS1: PINS1; smax =-10000; If (endgaps) { for (col0[0] = dely[0] = -insO, yy= l;yy<= leal; yy++) { eolO[yy] = dely[yy] = colO[yy-l] - insl; ndely[yy] = yy; > col0[0] = 0; /* Waterman Bull Math Biol 84 */ } else for (yy *> 1; yy <= lenl; yy++) dely[yy] = -insO; /* fill in match matrix ♦/ for (px = seqx[0], xx •» 1; xx <= lenO; px++, xx++) { /* initialize first entry in col */ if (endgaps) { if(xx — 1) coll[0] = delx = -(insO+msl); else coll [0] = delx = col0[0] - insl; ndelx = xx; } else { coll[0] = 0; delx «= -insO; ndelx = 0; 49 5 10 15 20 25 30 35 40 45 50 55 Table 1 (contQ ...nw for (py=seqxfl], yy *= 1; yy <= lenl; py++, yy++) { mis = colO[yy-l]; if (dna) mis += (xbm[*px-'A']&xbtn[*py-'A'])? DMAT: DMIS; else mis += _day[*px-'A'][*py-'A'3; /* update penalty far del in x seq; * favor new del oyer otigong del * ignore MAXGAP if weighting endgaps #/ if (endgaps || ndelyfry] < MAXGAP) { if (col0[yy] - insO >= dely[yy]) { dely[yy]=colO[yy] - (insO+insl); ndely[yy] = 1; } else { dely[yy] -=insl; ndely[yy]++; }else{ if (colOfyy] - (insO+insl) >= dely[yy]) { dely[yy] = colO[yy] - (insO+insl); ndely[yy] = 1; } else ndely[yy]++; ) /* update penalty for del in y seq; * favor new del over ongong del */ if (endgaps |J ndelx < MAXGAP) { if (coll[yy-l] - insO >= delx) { delx = coll[yy-i] - (insO+insl); ndelx=l; } else { delx -= insl; ndelx++; } else { if (coll[yy-l] - (insO+insl) >= delx) { delx = coll[yy-l] - (insO+insl); ndelx =1; } else ndelx++; } /* pick the maximum score; we're favoring * mis over any del and delx over dely *1 ...IIW id = xx - yy + lenl - 1; if (mis >= delx && mis >= delyfyy]) coll[yy]=mis; 50 Table lfcontn else If (delx >= delyfyy]) { colltyy] ■= delx; g - dx[id].ijmp; If (dx[id].jp.n[0] && (Idna || (ndelx >= MAXJMP && xx > dx[id].jp.x[ij]+MX) || mis > dx[id].score+DINSO)) { dx[id].ijmp++; if (++ij>= MAXJMP) { writejmps(id); ij = dx[id].ijmp = 0; dxfidj.offset = offset; offset += s!zeof(struct jmp) + sizeof(offset); } } dx[id].jp.n[ij] = ndelx; dx[id].jp.x[ij] = xx; dx[id].score=delx; } else { coll[yy] = delyfyy]; ij = dx[id].ijmp; If (dx[id].jpji[0] && (Idna || (ndely[yy] >= MAXJMP &&xx> dx[id].jpjt[ij]+MX) || mis > dx|1d].sco«H-DINS0)) { dx[idl.ijmp++; If (++ij>= MAXJMP) { writejmps(id); ij = dx[id].ijmp = 0; dx[id].offset = offeet; offeet += sizeof(struct jmp) + sizeof(offeet); } } dx[id].jp.n[ij] = -ndely[yy]; dx[id].jp.x[ij] = xx; dx[id].score=dely[yy]; } if (xx = lenO && yy < lenl) { /* last col */ if (endgaps) colltyy] — insO+insl*(lenl-yy); if(coll[yy]>smax){ smax = collfyy]; dmax = id; } if (endgaps && xx < lenO) coll[yy-l] -= insO+insl *(len0-xx); if (coll[yy-l] > smax) { smax=coll[yy-l]; dmax = id; } tmp = colO; colO « coll; coll = tmp; } (void) free((char *)ndely); (void) free((char *)dely); (void) free((char *)col0); (void) free((char *)coll); } 51 5 10 15 20 25 30 35 •«. 45 Table 1 fcont^ I* * * print() - only routine visible outside this module * •static: * getmatO — trace back best path, count matches: print() * pr_alignO - print alignment of described in array pQ: printO * dumpblockO - dump a block of lines with numbers, stars: pr_align0 * numsO — put out a number line: dumpblockQ * pudineO - put out a line (name, [numj, seq, [num]): dumpblockO * starsQ --put a line of stars: dumpblockO * stripnameO — strip any path and prefix from a seqname #/ ^include "nw.h" #define SPC 3 #define P_LINE 256 /* maximum output line */ #deilne P_SPC 3 /* space between name or num and seq */ extern _day[26][26]; int olen; /* set output line length */ FILE *fx; /* output file */ printQ print { int lx, ly, firstgap, lastgap; /* overlap */ if ((fe = fopen(ofile, "w")) = 0) { fprintf(stderr,"%s: can't write %s\n1', prog, ofile); cleanup(l); } fprintf(fx, "<first sequence: %s (length = %d)\n", namex[0], lenO); fprintf(fx, "<second sequence: %s (length - %d)\n", namexfl], lenl); olen=60; lx = lenO; ly = lenl; firstgap = lastgap = 0; if (dmax < lenl -1) { /* leading gap in x */ pp[0].spc = firstgap = lenl - dmax - 1; ly-=pp[0].spc; } else if (dmax > lenl - 1) { /* leading gap in y */ pp[l].spc = firstgap = dmax - (lenl -1); lx-=pp[l].spc; } If (dmaxO < lenO -1) { /* trailing gap in x */ lastgap = lenO - dmaxO -1; lx -= lastgap; } else if (dmaxO > lenO -1) { /* trailing gap in y */ lastgap = dmaxO - (lenO -1); ly — lastgap; } getmat(lx, ly, firstgap, lastgap); pr_alignO; } 52 Table 1 (cont^ /* * trace badk the best path, count matches */ static 5 getmatflx, ly, firstgap, lastgap) getmat int lx, ly; /* "core" (minus endgaps) */ int firstgap, lastgap; /* leading trailing overlap *1 { int nm, iO, il, sizO, sizl; 10 outx[32]; double pet; register nO, nl; register char *pO, *pl; /* get total matches, score 15 */ iO = il = sizO = sizl = 0; pO = seqx[0] + pp[l].spc; ^ pi = seqx[l] + pp[0].spc; W nO-=pp[l].spc +1; 20 nl = pp[0].spc +1; nm = 0; while (*p0 && *pl) { if(siz0) { pi++; 25 nl++; sizO—; } else if (sizl) { p0++; 30 nO++; sizl- } else { if (xbm[*pO-'A']&xbm[*p l-'A']) 35 nm++; if (nO++ = pp[0].x[i0]) sizO = pp[0].np0++); . if (nl++ — pp[l].x[il]) P sizl =pp[l].n[il++]; 40 . pO++; pi++; } 45 /* pot homology: * if penalizing endgaps, base is the shorter seq * else, knock off overhangs and take shorter core */ it (endgaps) 50 lx = (lenO < lenl)? lenO : lenl; else lx = (lx < ly)? lx: ly, pct= 100.*(double)nm/(double)lx; fprintfiffx, "\n"); 55 fjprintf(fx, "<%d match%s in an overlap of %d: %.2f percent similarity\n", nm, (nm= 1)? "": "es", lx, pet); 53 5 10 15 20 25 30 35 •40 45 50 55 Table 1 (cont't fprintf(fx, "<gaps in first sequence: %d", gapx); ...getmat if(gapx){ (void) sprintf(outx," (%d %s%s)\ ngapx, (dna)? "base":"residue", (ngapx — 1)? "":"s"); iprintf(fx,n%s", outx); iprintf(fic,H, gaps in second sequence: %d", gapy); if(gapy){ (void) sprintf^outx," (%d %s%s)", ngapy, (dna)? "base":"residue", (ngapy = 1)? "":"s"); iprintf(ix,,'%s", outx); } if (dna) fprintf(:fx, "\n<score: %d (match = %d, mismatch=%d, gap penalty = %d + %d per base)\n", smax, DMAT, DMIS, DINSO, DINS1); else §>rintf(fic, "\n<score: %d (DayhofF PAM 250 matrix, gap penalty = %d + %d per residue)\n", smax, PINS0, PINS1); if (endgaps) fprintf(fx, "<endgaps penalized left endgap: %d %s%s, right endgap: %d %s%s\n", firstgap, (dna)? "base": "residue", (firstgap =» 1)? "": "s", lastgap, (dna)? "base" : "residue", (lastgap = 1)? "": "s"); else fprintf(fx, "<endgaps not penalized\n"); } static nm; /* matches in core — for checking */ static lmax; /* lengths of stripped file names */ static ij[2]; /* jmp index for a path */ static nc[2]; /* number at start of current line */ static ni[2]; /* current elem number — for gapping *1 static siz[2]; static char *ps[2]; I* ptr to current element */ static char *po[2]; /* ptr to next output char slot */ static char out[2][P_LINE]; /* output line */ static char star[P_LINE]; /* set by starsO */ /* * print alignment of described in struct path pp[] */ static pr_alignQ pr_align { int nn; /* char count*/ int more; register i; for (i = 0, hnax^O; i <2; i++) { nn = stripname(namex[i]); if(nn>hnax) lmax = nn; nc[i] = l; ni[i]=l| siz[i] = ij[i] = 0; ps[i] ■= seqx[i]; po[i] = out[i]; } 54 5 . . 1.0 15 20 25 30 35 40 45 50 55 Table 1 fcontn for (nn=mn=0, more = 1; more;) { ...p*_align for (i = more = 0; i < 2; B-+) { I* * do we have more of this sequence? */ if (!*ps[i]) continue; more++; if (pp[i].spc) { /* leading space */ ♦po[i]++ = "; pp[i].spc-; } elseif(sizp]) { /* in a gap */ *po[i]++ = '-1; step]-; } else { /* we're putting a seq dement *1 *po[i] = *ps[i]; if (islower(*ps[i])) *psp] = toupper(*ps[i]); po[i]++; ps[i]++; /* * are we at next gap for this seq? */ lf(nip]=ppp].xpjp]]){ t* * we need to merge all gaps * at this location *1 siz[i] = pp[i].n[ij[i]++]; while (nip]=pp[i].x[ij[i]]) siz[i] += pp[i].n[ijti]++]; } nip]++; } } if(++nn = olenj| Imore && nn) { dumpblockO; for(i=0;i<2;i++) pop] = outp]; nn = 0; } } } /* * dump a block of lines, including numbers, stars: pr_align0 */ static dumpblockO dumpblock {. register i; for(i = 0;i<2;H-+) *Pop]~ = '\0'; 55 5 10 15 20 25 30 35 40 45 50 55 Table 1 fcont') (void) putcOn', fx); for(i™0;i<2;i++){ if (*out[i] && (*out[i] !='' || *(P°B]) 1='')) { if(i = 0) nums(i); if (i = 0 && *out[l]) putline(i); if (i = 0 && *out[l]) fprintf(fx, star); » 0 = 1) nums(i); } /* * put out a number line: dumpblockO */ static nums(ix) int ix; /* index in out[] holding seq line */ { char nline[P_LINE]; register i, j; register char *pn, *px, *py; for (pn = nline, i = 0; i < lmax+P_SPC; i++, pn++) *pn =1'; for (i = ncfix], py=out[ix]; *py; py++, pn++) { = "ll*py='-') if (*py = else { *pn="; if (i%l 0 = 0 || (i = 1 && nctix] != 1)) { j = (i<0)?-i:i; for (px«=pn;j;j/= 10, px~) *px=j%10 + '0'; if (i < 0) >* dumpblock nums *px = '-'; } *pn = "; } m-; *pn=W; nc[ix] = i; for (pn = nline; *pn; pn++) (void) putc(*pn, fo); (void) putcCVn', fe); /* * put out a line (name, [num], seq, [num]): dumpblockO */ static putline(ix) int ix; { putline 56 5 10 15 20 25 30 35 40 45 50 55 Table 1 fcont') ...putline int i; register char *px; for (px = namexfix], i ■ 0; *px && *px !=*px++, i++) (void) putc(*px, 6c); for (; i < linax+P_SPC; i++) (void) putcCfic); I* these count from 1: * niQ is current element (from 1) * ncQ is number at start of current line */ for (px = out[ix]; *px; px++) (void) putc(*px&0x7F, fx); (void) putcCW, fic); } /* * put a line of stars (seqs always in out[0], out[l)): dumpblockO */ static starsO stars { int i; register char *p0, *pl, cx, *px; if (!*out[0] || (*out[0] = "&& *(po[0]) = ")|| !*out[l] |j (*out[l] ='' && *(po[l]) ='')) return; px = star; for (i = lmax+P_SPC; i; i—) *px++ =''; for (pO ■» out[0], pi = out[l]; *p0 && *pl; pO++, pl++) { if (isalpha(*p0) && isalpha(*pl)) { if (xbm[*p0-A']&xbm[*p 1 -'A']) { cx = nm++; } else if (Idna && _day[*pO-,A'][*pl-,A'] > 0) cx = V; else cx = "; } else cx="; *px++ = cx; } . *px++=V; *px® W; } 57 Table 1 (contn /* * strip path or prefix from pn, return len: pr_alignO */ static 5 stripname(pn) stiipname char *pn; /* file name (may be path) */ { register char *px, *py; 10 py = 0; . . .. . for (px=pn; *px; px++) if (*px =='/■) py = px+l; tf(py) 15 (void) strepy(pn, py); return(strien(pn)); 20 f. 58 5 10 15 20 25 30 35 40 45 Table 1 (contM * cleanupO -- cleanup any tmp file * getseqO - read in seq, set dna, len, maxlen * gjjallocO — callocO with error checkin * readjmpsO - get the good jmps, from tmp file if necessary * writejmpsO - write a filled array of jmps to a tmp file: nwO */ include "nw.h" ^include <sys/file.l£> char *jname = "/tmp/homgXXXXXX"; FILE *fi; int cleanupO; long lseekO; /# * remove any tmp file if we blow */ cleanup© int i; { (void) unlink(jname); exit(i); } /* * read, return ptr to seq, set dna, len, maxlen * skip lines starting with'<■, or '>' * seq in upper or lower case */ char * getseq(fHe, len) char *file; /* file name*/ int *len; /* seq len */ { /* tmp file for jmps*/ /* cleanup tmp file */ cleanup getseq char line[1024], *pseq; register char *px, *py; int natgc, tlen; FILE *fp; if ((fp = fopen(file,"r")) — 0) { fprintf(stderr,''%s: can't read %s\n", prog, file); exit(l); } tlen = natgc = 0; while (fgets(line, 1024, fp)) { if (*line = ';' || *line = '<' || *line = '>') continue; for (px = line; *px 1= V; px++) if (isupper(*px) || islower(*px)) tlerrB-; } if ((pseq=malloc((unsigned)(tlen+6))) = 0) { fprintf(stderr,''%s: mallocO Med to get %d bytes for %s\n", prog, tlen+6, file); exit(l); } pseq[0] = pseq[l] = pseq[2] = pseq[3] = "W; 59 5 JO 15 20 25 30 35 40 45 50 55 Table 1 fconn py = pseq + 4; ♦len «* tlen; rewind(fp); while (fgetsQine, 1024, lp)) { if (*line =|| "line «= '<* || "line=">') continue; for (px = line; "px != V; px++) { if (isupper(*px)) *py++ = *px; else If (islower(*px)) *py-H-=toupper(*px); if (index("ATGCU\*(py-1))) natgc-H-; } } *py++ = *\0'; *py = "\0'; (void) fclose(fp); dna = natgc > (tlen/3); rcturn(pseq+4); } char * g_calloc(msg, nx, sz) char *msg; int nx, sz; /* program, calling routine */ /* number and size of elements */ { .getseq gcalloc char *px, *callocO; if ((px = calloc((unsigned)nx, (unslgned)sz)) == 0) { if (*msg) { iprintf^stderr, "%s: g_calloc() failed %s (n=%d, sz=%d)\n", prog, msg, nx, sz); exit(l); } } return(px); /* * get final jmps from dxQ or tmp file, set pp[], reset dmax: mainO ♦/ readjmpsO readjjnps { int fd=-l; int siz, iO, il; register i,j,xx; if 03) { (void) fclose(Q); if ((fd = openQname, OJRDONLY, 0)) < 0) { fprintflCstdeir, "%s: can't qpen() %s\n", prog, jname); cleanup(l); } } for (i = iO = il = 0, dmaxO = dmax, xx = lenO;; i++) { while (1){ for (j = dx[dmax].ijmp; j >= 0 && dx[dmax] jp.xQ] >= xx; j~) 60 Table 1 (cont^ ...readjmps If <j < 0 && dx[dmax].offset && ij) { (void) lseek(fd, dx[dmax] .offset, 0); (void) read(fd, (diar *)&dx[dmax].jp, sizeof(struct jmp)); 5 (void) read(fd, (diar *)&dx[dmax].offset, sizeof(dx[dmax].offset)); dx[dmax].ijmp = MAXJMP-1; } else break; } if (i >= JMPS) { 10 fprintf(stderr, "%s: too many gaps in alignments", prog); cleanup(l); if (j >= 0) { siz «■ dx[dmax].jp.n[j3; 15 xx = dx[dmax].jp.x[j]; dmax += siz; if (siz < 0) { /* gap in second seq */ pp[l]ji[il] = -«iz; fc xx+=siz; F20 /* id = xx - yy+lenl - 1 */ pp[l].x[il] = xx - dmax + lenl -1; gapy++; ngapy -= siz; /* ignore MAXGAP when doing endgaps */ 25 siz=(-siz < MAXGAP || endgaps)? -siz: MAXGAP; il++; } else if (siz > 0) { /* gap in first seq */ pp[0].n[i0] = siz; 30 pp[0].x[i0] = xx; gapx++; ngapx += siz; /* ignore MAXGAP when doing endgaps */ siz=(siz < MAXGAP || endgaps)? siz: MAXGAP; 35 i0++; } else break; *0 } /* reverse the order of jmps */ for 0' = 0, iO—; j < iO; j++, i0~) { i = pp[0].n0]; pp[0].nD] = pp[0].n[i0]; pp[0].np0] = i; i = pp[0].x[j]; pp[0].x[j] = pp[0].x[i0]; pp[0].x[i0] = i; 45 } for (j = 0, il—; j < il; j++, il~) { i = pp[l].nD3; pp[l]-n[j] = pp[l].n[il]; pp[l].n[il] = i; i = pp[l].x01; PP[l].xD] = pp[l].x[il]; pp[l].x[il] = i; } 50 if (fd >= 0) (void) close(fd); if(fl){ (void) unlink(jname); fl = 0; 55 offeet =0; > } 61 TafrUe I (eont') /* * write a filled jmp struct offset of the prev one (if any): nwO */ writejmps(ix) fait ix; { char *mktempO; . ... . . . . if (mktempQname) < 0) { fprintf(stderr, "%s: cantmktempO %s\nH, prog, jname); cleanup(l); } if ((fj = fopenflname, "w")) = 0) { fpiintf(stderr, "%s: cant write %s\n", prog, jname); exit(l); } } (void) fwrite((char *)&dx[ix].jp, sizeof(struct jmp), 1, fl); (void) fwrite((char *)&dx[ix].offset, s!zeof(dx[ix].of&et), 1, fl); } 62 Table 2 TAT XXXXXXXXXXXXXXX (Length = 15 amino acids) Comparison Protein XXXXXYYYYYYY • (Length =12 amino acids) % amino acid sequence identity = (the number of identically matching amino acid residues between the two polypqptide sequences as determined by ALIGN-2) divided by (the total number of amino acid residues of the TAT polypqptide) = 5 divided by 15 = 33.3% Table 3 TAT XXXXXXXXXX (Length = 10 amino acids) Comparison Protein XXXXXYYYYYYZZYZ (Length = 15 amino acids) % amino acid sequence identity = (the number of identically matching amino acid residues between the two polypeptide sequences as determined by AIIGN-2) divided by (the total number of amino acid residues of the TAT polypqptide) = 5 divided by 10 = 50% Table 4 TAT-DNA NNNNNNNNNNNNNN (Length® 14 nucleotides) Comparison DNA NNNNNNLLLLLLLLLL (Length = 16 nucleotides) % nucleic acid sequence identity = (the number of identically matching nucleotides between the two nucleic acid sequences as determined by ALIGN-2) divided by (the total number of nucleotides of the TAT-DNA nucleic acid sequence) = 6 divided by 14 = 42.9% 63 Table 5 TAT-DNA NNNbHSINNNNNNN (Length = 12 nucleotides) Comparison DNA NNNNLLLW (Length = 9 nucleotides) % nucleic acid sequence identity = (the number of identically matching nucleotides between the two nucleic acid sequences as determined by ALIGN-2) divided by (the total number of nucleotides of the TAT-DNA nucleic acid sequence) = 4 divided by 12 = 33.3% n. Compositions and Methods of the Invention A. Anti-TAT Antibodies Described are anti-TAT antibodies which may find use herein as therapeutic and/or diagnostic agents. Exemplary antibodies include polyclonal, monoclonal, humanized, bispecific, and heteroconjugate antibodies. 1. Polyclonal Antibodies Polyclonal antibodies are preferably raised in animals by multiple subcutaneous (sc) or intraperitoneal (ip) injections of the relevant antigen and an adjuvant It may be useful to conjugate the relevant antigen (especially when synthetic peptides are used) to a protein that is immunogenic in the species to be immunized. For example, the antigen can be conjugated to keyhole limpet hemocyanin (KLH), serum albumin, bovine thyroglobulin, or soybean trypsin inhibitor, using a bifunctional or derivatizing agent, e.g., maleimidobenzoyl sulfosuccinimide ester (conjugation through cysteine residues), N-hydroxysuccinimide (through lysine residues), glutaraldehyde, succinic anhydride, SOCl2, or R1N=C=NR, where R and Rl are different alkyl groups. Animal'! are immunized against the antigen, immunogenic conjugates, or derivatives by combining, e.g., 100 jig or 5 |xg of the protein or conjugate (for rabbits or mice, respectively) with 3 volumes of Freund's complete adjuvant and injecting the solution intradermally at multiple sites. One month later, the animals are boosted with 1/5 to 1/10 the original amount of peptide or conjugate in Freund's complete adjuvant by subcutaneous injection at multiple sites. Seven to 14 days later, the animals are bled and the serum is assayed for antibody titer. Animals are boosted until the titer plateaus. Conjugates also can be made in recombinant cell culture as protein fusions. Also, aggregating agents such as alum are suitably used to enhance the immune response. 2. Monoclonal Antibodies Monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., Nature. 256:495 (1975), or may be made by recombinant DNA methods (U.S. Patent No. 4,816,567). In the hybridoma method, a mouse or other appropriate host animal, such as a hamster, is immunized as described above to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization. Alternatively, lymphocytes may be immunized in vitro. After 64 immunization, lymphocytes are isolated and then fused with a myeloma cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp.59-103 (Academic Press, 1986)). The hybridoma cells thus prepared are seeded and grown in a suitable culture medium which medium preferably contains one or more substances that inhibit the growth or survival of the unfiised, parental myeloma 5 cells (also referred to as fusion partner). For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the selective culture medium for the hybridomas typically will includehypoxanthine, aminopterin, and thymidine (HAT medium), which substances preventthe growth of HGPRT-deficient cells. Preferred fusion partner myeloma cells are those that fuse efficiently, support stable high-level production 10 of antibody by die selected antibody-producing cells, and are sensitive to a selective medium that selects against the unfiised parental cells. Preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-11 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, California USA, and SP-2 and derivatives e.g., X63-Ag8-653 cells available from the American Type Culture Collection, Manassas, Virginia, USA. Human myeloma and mouse-human heteromyeloma cell lines also have been 15 described for the production ofhuman monoclonal antibodies (Kozbor. J. Immunol.. 133:3001 (1984); andBrodeur et al., Monoclonal Antibody Production Techniques and Applications, pp. 51-63 (Marcel Dekker, Inc., New York, 1987)). Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by hybridoma 20 cells is detennined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis described in Munson et al., Anal. Biochem.. 107:220 (1980). Once hybridoma cells that produce antibodies of the desired specificity, affinity, and/or activity are 25 identified, the clones may be subclonedby limiting dilution procedures and grown by standard methods (Goding, ) Monoclonal Antibodies: Principles and Practice, no.59-103 (Academic Press, 1986)). Suitableculturemediaforthis purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal e.g„ by i.p. injection of the cells into mice. The monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, 30 ascites fluid, or serum by conventional antibody purification procedures such as, for example, affinity chromatography (e.g., using protein A or protein G-Sepharose) or ion-exchange chromatography, hydroxylapatite chromatography, gel electrophoresis, dialysis, etc. DNA encoding the monoclonal antibodies is readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the 35 heavy and light chains of murine antibodies). The hybridoma cells serve as a preferred source of such DNA. Once isolated, the DNA may be placed into expression vectors, which are then transfected into host cells such as R coli cells, simian COS cells, Chinese Hamster Ovary (CHO) cells, or myeloma cells that do not otherwise produce 65 antibody protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. Review articles to* on recombinant expression in bacteria of DNA encoding the antibody include Skerra et al., Curr. Opinion in Immunol.. 5:256-262 (1993) and Pliickthun, Immunol. Revs. 130:151-188 (1992). In a further embodiment, monoclonal antibodies or antibody fragments can be isolated from antibody phage libraries generated using Ihe techniques described inMcCafferty et al., Nature. 348:552-554 (1990). Clackson etal.. Nature. 352:624-628 (1991) andMarks etaLJ.Mol.Biol.. 222:581-597(1991) describe the isolation of murine and human antibodies, respectively, using phage libraries. Subsequent publications describe the production of high affinity (nM range) human antibodies by chain shuffling (Maries et al., Bio/Technology. 10:779-783 (1992)), as well as combinatorial infection and in vivo recombination as a strategy for constructing very large phage libraries (Waterhouse et al., Nuc. Acids. Res. 21:2265-2266 (1993)). Thus, these techniques are viable alternatives to traditional monoclonal antibody hybridoma techniques for isolation of monoclonal antibodies. Ihe DNA that encodes the antibody may be modified to produce chimeric or fusion antibody polypeptides, for example, by substituting human heavy chain and light chain constant domain (CH Mid Cj) sequences for the homologous murine sequences (U.S. Patent No. 4,816,567; and Morrison, et al., Proc. Natl Acad. Sci. USA. 81:6851 (1984)), or by fusing the immunoglobulin coding sequence with all or part of the coding sequence for a non-immunoglobulin polypeptide (heterologous polypeptide). The non-immunoglobulin polypeptide sequences can substitute for the constant domains of an antibody, or they are substituted for the variable domains of one antigen-combining site of an antibody to create a chimeric bivalent antibody comprising one antigen-combining site having specificity for an antigen and another antigen-combining site having specificity for a different antigen. 3. Human and Humanized Antibodies The described anti-TAT antibodies may further comprise humanized antibodies or human antibodies. Humanized forms of non-human (e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature. 321:522-525 (1986); Riechmann et al., Nature. 222:323-329 (1988); and Presta, Curr. Op. Struct Biol.. 2:593-596 (1992)]. Methods for humanizing non-human antibodies are well known in the art Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non- 66 human amino acid residues are often referred to as "import" residues, which are typically taken from an "import" variable domain. Humanization can be essentially performed following the method of Winter and co-workers [Jones et al., Nature. 321:522-525 (1986); Riechmann et al., Nature. 332:323-327 (1988); Verhoeyen etal, Science. 239:1534-1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such "humanized" antibodies are chimeric antibodies (U.S. Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies. The choice of human variable domains, both light and heavy, to be used in making the humanized antibodies is very important to reduce antigenicity and HAMA response (human anti-mouse antibody) when the antibody is intended for human therapeutic use. According to the so-called "best-fit" method, the sequence of the variable domain of a rodent antibody is screened against the entire library of known human variable domain sequences. The human V domain sequence which is closest to that of die rodent is identified and the human framework region (FR) within it accepted for the humanized antibody (Sims et aL, J Tmmnnnl. 151:2296 (1993); Chothia et al., J. Mol. Biol.. 196:901 (1987)). Another method uses a particular framework region derived from the consensus sequence of all human antibodies of a particular subgroup of light or heavy chains. The same framework may be used for several differenthumanized antibodies (Carter etal.. Proc. Natl. Acad. Sci. USA. 89:4285 (1992); Presta et al., J. Immunol. 151:2623 (1993)). It is further important that antibodies be humanized with retention of high binding affinity for the antigen and other favorable biological properties. To achieve this goal, according to a preferred method, humanized antibodies are prepared by a process of analysis of the parental sequences and various conceptual humanized products using three-dimensional models of the parental and humanized sequences. Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art Computerprograms are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen, hi this way, FR residues can be selected and combined from the recipient and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigesn(s), is achieved. In general, the hypervariable region residues are directly and most substantially involved in influencing antigen binding. Various forms of a humanized anti-TAT antibody are contemplated. For example, the humanized antibody may be an antibody fragment, such as a Fab, which is optionally conjugated with one or more cytotoxic agent(s) in order to generate an immunoconjugate. Alternatively, the humanized antibody may be an intact antibody, such as an intact IgGl antibody. As an alternative to humanization, human antibodies can be generated. For example, it is now possible to produce transgenic animals (e.g., mice) that are capable, upon immunization, of producing a full repertoire of human antibodies in the absence of endogenous immunoglobulin production. For example, it has been described 67 {bat the homozygous deletion of the antibody heavy-chain joining region (Jjg) gene in chimeric and gam-line mutant mice results in complete inhibition of endogenous antibody production. Transfer of the human germ-line immunoglobulin gene array into such germ-line mutant mice will result in the production ofhuman antibodies upon antigen challenge. See, e.g., Jakobovits et al. Proc. Natl. Acad. Sci. USA. 90:2551 (1993); Jakobovits etal.. Nature. 362:255-258 (1993); Braggemann etal, YMrm^muno,7:33 (1993); U.S. PatentNos. 5,545,806,5,569,825,5,591,669 (all of GenPharm); 5,545,807; and WO 97/17852. Alternatively, phage display technology (McCafferty et al., Nature 348:552-553 [1990]) can be used to produce human antibodies and anybody fragments in vitro, from immunoglobulin variable (V) domain gene repertoires from unimmunized donors. According to this technique, antibody V domain genes are cloned in-frame into either a major or minor coat protein gene of a filamentous bacteriophage, such as M13 or fd, and displayed as functional antibody fragments on the surface of the phage particle. Because the filamentous particle contains a single-stranded DNA copy of the phage genome, selections based on the functional properties of the antibody also result in selection of the gene encoding the antibody exhibiting those properties. Thus, the phage mimics some of the properties of the B-cell. Phage display can be performed in a variety of formats, reviewed in, e.g., Johnson. Kevin S. and ChiswelL David J.. Current Opinion in Structural Biology 3:564-571 (1993). Several sources of V-gene segments can be used for phage display. Clackson et al., Nature. 352:624-628 (1991) isolated a diverse array of anti-oxazolone antibodies from a small random combinatorial library of V genes derived from the spleens of immunized mice. A repertoire of V genes from unimmunized human donors can be constructed and antibodies to a diverse array of antigens (including self-antigens) can be isolated essentially following the techniques describedbv Marks et al.. J. Mol. Biol. 222:581-597 (19911 or Griffith et al.. EMBO J. 12:725-734 (1993V See, also. U.S. PatentNos. 5,565,332 and 5,573,905. As discussed above, human antibodies may also be generated by in vitro activated B cells (see U.S. Patents 5,567,610 and 5,229,275). 4. Antibody fragments In certain circumstances there are advantages of using antibody fragments, rather than whole antibodies. The smaller size of the fragments allows for rapid clearance, and may lead to improved access to solid tumors. Various techniques have been developed for the production of antibody fragments. Traditionally, these fragments were derived via proteolytic digestion of intact antibodies (see, e.g., Morimoto et al., Journal of Biochemical and Biophysical Methods 24:107-117 (1992); and Brennan et al.. Science. 229:81 (1985)). However, these fragments can now be produced directly by recombinant host cells. Fab, Fv and ScFv antibody fragments can all be expressed in and secreted from E. coli, thus allowing the facile production of large amounts of these fragments. Antibody fragments can be isolated from the antibody phage libraries discussed above. Alternatively, Fab'-SH fragments can be directly recovered from£ coli and chemically coupled to fotmF(abl)2 fragments (Carter et al., Bio/Technology 10:163-167 (1992)). According to another approach, F(ab')2 fragments can be isolated directly from recombinant host cell culture. Fab and F(ab')2 fragment with increased in vivo half-life comprising a salvage receptor binding epitope residues are described in U.S. Patent No. 5,869,046. Other techniques for the production of antibody fragments will be apparent to the skilled practitioner. In other embodiments, the antibody of choice is a single chain Fv fragment (scFv). See WO 93/16185; U.S. Patent No. 5,571,894; andU.S. Patent No. 68 5,587,458. Fv and sFv are the only species with intact combining sites that ate devoid of constant regions; thus, they are suitable for reduced nonspecific binding during in vivo use. sFv fusion proteins may be constructed to yield fusion of an effector protein at either the amino or the caiboxy terminus of an sFv. See Antibody Engineering, ed. Borrebaeck, supra. The antibody fragment may also be a 'linear antibody", e.g, as described in U.S. Patent 5,641,870 for example. Such linear antibody fragments may be monospecific or bispecific. 5. Bispecific Antibodies Bispecific antibodies are antibodies that have binding specificities for at least two different epitopes. Exemplary bispecific antibodies may bind to two different epitopes of a TAT protein as described herein. Other such antibodies may combine a TAT binding site with a binding site for another protein. Alternatively, an anti-TAT arm may be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD3), or Fc receptors for IgG (FcyR), such as FcyRI (CD64), FcyRII (CD32) and FcyRHI (CD16), so as to focus and localize cellular defense mechanisms to the TAT-expressing cell. Bispecific antibodies may also be used to localize cytotoxic agents to cells which express TAT. These antibodies possess a TAT-binding arm and an arm which binds the cytotoxic agent (e.g, saporin, anti-interferon-a, vinca alkaloid, ricin A chain, methotrexate or radioactive isotope hapten). Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g., F(ab')2 bispecific antibodies). WO 96/16673 describes a bispecific anti-ErbB2/anti-FcyRin antibody and U.S. Patent No. 5,837,234 discloses a bispecific anti-ErbB2/anti-FcyRI antibody. A bispecific anti-EibB2/Fca antibody is shown in W098/02463. U.S. Patent No. 5,821,337 teaches a bispecific anti-ErbB2/anti-CD3 antibody. Methods for making bispecific antibodies are known in the art Traditional production of foil length bispecific antibodies is based on the co-expression of two immunoglobulin heavy chain-light chain pairs, where the two chains have different specificities (Millstein et al., Nature 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of 10 different antibody molecules, of which only one has the correct bispecific structure. Purification of the correct molecule, which is usually done by affinity chromatography steps, is rather cumbersome, and the product yields are low. Similar procedures are disclosed in WO 93/08829, and in Traunecker et al.. EMBO J. 10:3655-3659 (1991). According to a different approach, antibody variable domains with the desired binding specificities (antibody-antigen combining sites) are fused to immunoglobulin constant domain sequences. Preferably, the. fusion is with an Ig heavy chain constant domain, comprising at least part of the hinge, C%2, and CH3 regions. It is preferred to have the first heavy-chain constant region (Cyl) containing the site necessary for light chain bonding, present in at least one of the fusions. DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host cell. This provides for greater flexibility in adjusting the mutual proportions of the three polypeptide fragments in embodiments when unequal ratios of the three polypeptide chains used in Ihe construction provide the optimum yield of the desired bispecific antibody. It is, however, possible to insert the coding sequences for two or all three polypeptide chains into a single expression vector when the expression of at least two polypeptide chains in equal ratios results in high yields or when the ratios have no significant affect 69 oaths yield of the desired chain combination. In a preferred embodiment of this approach, the bispecific antibodies are composed of a hybrid immunoglobulin heavy chain with a first binding specificity in one arm, and a hybrid immunoglobulin heavy chain-light chain pair (providing a second binding specificity) in the other arm. It was found that this asymmetric structure facilitates the separation of the desired bispecific compound from unwanted immunoglobulin chain 5 combinations, as die presence of an immunoglobulin light chain in only one half of Ihe bispecific molecule provides for a facile way of separation. This approach is disclosed in WO 94/04690. For fiirther details of ' generating bispecific antibodies see, for example, Suresh etal., Methods in Bnzvmoloev 121:210 (1986). According to another approach described in U.S. Patent No. 5,731,168, Ihe interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from 10 recombinant cell culture. The preferred interface comprises at least a part of the C%3 domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule ate replaced with laiger side chains (e.g, tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g, alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other 15 unwanted end-products such as homodimers. Bispecific antibodies include cross-linked or "heteroconjugate" antibodies. For example, one of the antibodies in the heteroconjugate can be coupled to avidin, the other to biotin. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Patent No. 4,676,980), and for treatment of HIV infection (WO 91/00360, WO 92/200373, and EP 03089). Heteroconjugate antibodies may be made using any 20 convenient cross-linking melhods. Suitable cross-linking agents are well known in the art, and are disclosed in U.S. Patent No. 4,676,980, along with a number of cross-linking techniques. Techniques for generating bispecific antibodies from antibody fragments have also been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al. Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab02 25 fragments. These fragments are reduced in the presence of the dithiol complexity agent, sodium arsenite, to stabilize vicinal dithiols and prevent intermolecular disulfide formation. Ihe Fab' fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab'-TNB derivatives is then reconverted to the Fab'-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the 3 0 selective immobilization of enzymes. Recent progress has facilitated the direct recovery of Fab'-SH fragments from E. coli, which can be chemically coupled to form bispecific antibodies. Shalaby et al, J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab')2 molecule. Each Fab' fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific 3 5 antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets. Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture 70 have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny etal.. J. Immunol. 148(5):1547-1553 (1992). The leucine zipperpeptides from the Fos and Jun proteins were linked to the Fab1 portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The "diabody" technology described by Hollinger et al., Proc. 5 Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a VH connected to a VL by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the V^ and Vl domains of one fragment are forced to pair with the complementary VL and Vh domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been 10 reported. See Gruber et al., J. Immunol.. 152:5368 (1994). Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be | prepared. Tutt et al., -T. Tmmiinol. 147:60 (1991). 6. Heteroconjugate Antibodies Heteroconjugate antibodies are also useful herein. Heteroconjugate 15 antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells [U.S. PatentNo. 4,676,980], and for treatment ofHTV infection [WO 91/00360; WO 92/200373; EP 03089]. It is contemplated that the antibodies may be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins may be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable 20 reagents for this purpose include iminothioiate and methyI-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Patent No. 4,676,980. 7. Multivalent Antibodies A multivalent antibody may be internalized (and/or catabolized) fester than a bivalent antibody by a cell expressing an antigen to which the antibodies bind. The antibodies of the present invention can be multivalent 25 antibodies (which are other than of the IgM class) with three or more antigen binding sites (e.g. tetravalent ) antibodies), which can be readily produced by recombinant expression of nucleic acid encoding the polypeptide chains of Ihe antibody. The multivalent antibody can comprise a dimerization domain and three or more antigen binding sites. The preferred dimerization domain comprises (or consists of) anFc region or a hinge region. In this scenario, the antibody will comprise an Fc region and three or more antigen binding sites amino-terxninal to the Fc 30 region. The preferred multivalent antibody herein comprises (or consists of) three to about eight, but preferably four, antigen binding sites. The multivalent antibody comprises at least one polypeptide chain (and preferably two polypeptide chains), wherein the polypeptide chain(s) comprise two or more variable domains. For instance, the polypeptide chain(s) may comprise VDl-(Xl)n-VD2-(X2)n-Fc, wherein VD1 is a first variable domain, VD2 is a second variable domain, Fc is one polypeptide chain of an Fc region, XI and X2 represent an amino acid or 35 polypeptide, and n is 0 or 1. For instance, the polypeptide chain(s) may comprise: VH-CHl-flexible linker-VH-CHl-Fc region chain; or VH-CH1-VH-CH1 -Fc region chain. The multivalent antibody herein preferably further comprises at least two (and preferably four) light chain variable domain polypeptides. The multivalent antibody herein may, 71 for instance, comprise from about two to about eight light chain variable domain polypeptides. The light chain variable domain polypeptides contemplated here comprise a light chain variable domain and, optionally, further comprise a CL domain. 8. Effector Function Engineering It may be desirable to modify an antibody with respect to effector function, e.g., so as to enhance antigen-dependent cell-mediated cyotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) of the antibody. This may be achieved by introducing one or more amino acid substitutions in an Fc region of the antibody; Alternatively or additionally, cysteine residue(s) may be introduced in the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated may have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). SeeCaron etal.. J. Exp Med. 176:1191-1195 (1992) and Shopes.B. J. Immunol. 148:2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity may also be prepared using heterobifunctional cross-linkers as described in Wolff et al., Cancer Research 53:2560-2565 (1993). Alternatively, an antibody can be engineered which has dual Fc regions and may (hereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design 3:219-230 (1989). To increase the serum half life of the antibody, one may incorporate a salvage receptor binding epitope into the antibody (especially an antibody fragment) as described in U.S. Patent 5,739,277, for example. As used herein, the tenn "salvage receptor binding epitope" refers to an epitope of the Fc region of an IgG molecule (e.g., IgGj, IgG2, IgG3, or IgG4) that is responsible for increasing the in vivo serum half-life of the IgG molecule. 9. Immunoconiuaates Also useful are immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, a growth inhibitory agent, atoxin(e.g., an enzymatically active toxin ofbacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate). Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleuritesfordii proteins, dianthin proteins, Phytolaca americana proteins CP API, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include 212Bi, 13II, I31In, ®°Y, and mRe. Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al, Science. 238:1098 (1987). Carbon-14-labeled l-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of 72 radionucleotide to the antibody. See W094/11026. Conjugates of an antibody and one or more small molecule toxins, such as a calicheamicin, maytansinoids, a trichothene, and CC1065, and the derivatives of these toxins that have toxin activity, are also contemplated herein. Maytansine andmavtansinoids In one preferred embodiment, an anti-TAT antibody (full length or fragments) is conjugated to one or more maytansinoid molecules. Maytansinoids are mitototic inhibitors which act by inhibiting tubulin polymerization. Maytansine was first isolated from the east African shrub Maytenus serrata (U.S. Patent No. 3,896,111). Subsequently, it was discovered that certain microbes also produce maytansinoids, such as maytansinol and C-3 maytansinol esters (U.S. Patent No. 4,151,042). Synthetic maytansinol and derivatives and analogues thereof are disclosed, for example, inU.S. PatentNos. 4,137,230; 4,248,870; 4,256,746; 4,260,608; 4,265,814; 4,294,757; 4,307,016; 4,308,268; 4,308,269; 4,309,428; 4,313,946;4,315,929,'4,317,821; 4,322,348; 4,331,598;4,361,650; 4,364,866; 4,424,219; 4,450,254; 4,362,663; and 4,371,533, the disclosures of which are hereby expressly incorporated by reference. Mavtansmoid-antibodv conjugates In an attempt to improve their therapeutic index, maytansine and maytansinoids have been conjugated to antibodies specifically binding to tumor cell antigens. Immunoconjugates containing maytansinoids and their therapeutic use are disclosed, for example, inU.S. PatentNos. 5,208,020,5,416,064 and European Patent EP 0 425 235 Bl, the disclosures of which are hereby expressly incorporated by reference. Liu et al., Proc. Natl. Acad. Sci. USA 93:8618-8623 (1996) described immunoconjugates comprising a maytansinoid designated DM1 linked to the monoclonal antibody C242 directed against human colorectal cancer. The conjugate was found to be highly cytotoxic towards cultured colon cancer cells, and showed antitumor activity in an in vivo tumor growth assay. Chari et al., Cancer Research 52:127-131 (1992) describe itntnunoconjugates in which a maytansinoid was conjugated via a disulfide linker to the murine antibody A7 binding to an antigen on human colon cancer cell lines, or to another murine monoclonal antibody TA1 that binds the HER-2/neu oncogene. The cytotoxicity of the TA.1-maytansonoid conjugate was tested in vitro on the human breast cancer cell line SK-BR-3, which expresses 3 x 10s HER-2 surface antigens per cell. The drag conjugate achieved a degree of cytotoxicity similar to the free maytansonid drug, which could be increased by increasing the number of maytansinoid molecules per antibody molecule. The A7-maytansinoid conjugate showed low systemic cytotoxicity in mice. Anti-TAT polypeptide antibodv-mavtansinoid conjugates (immunoconiugates) Anti-TAT antibody-maytansinoid conjugates are prepared by chemically linking an anti-TAT antibody to a maytansinoid molecule without significantly diminishing the biological activity of either the antibody or the maytansinoid molecule. An average of 3-4 maytansinoid molecules conjugated per antibody molecule has shown efficacy in enhancing cytotoxicity of target cells without negatively affecting the function or solubility of the antibody, although even one molecule of toxin/antibody would be expected to enhance cytotoxicity over the use of naked antibody. Maytansinoids are well known in ihe art and can be synthesized by known techniques or isolated from natural sources. Suitable maytansinoids are disclosed, for example, inU.S. PatentNo. 5,208,020 and in the other patents and nonpatent publications referred to hereinabove. Preferred maytansinoids are maytansinol 73 and maytansinol analogues modified in (he aromatic ring or at other positions of the maytansinol molecule, such as various maytansinol esters. There are many linking groups known in the art for making antibody-maytansinoid conjugates, including, for example, those disclosed in U.S. Patent No. 5,208,020 or EP Patent 0 425 235 Bl, and Chari et al., Cancer Research 52:127-131 (1992). The linking groups include disufide groups, thioether groups, acid labile groups, photolabile groups, peptidase labile groups, or esterase labile groups, as disclosed in the above-identified patents, disulfide and thioether groups being preferred. Conjugates of the antibody and maytansinoid may be made using a variety of bifunctional protein coupling agents such as N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP), succinimidyl-4-(N-maleimidomethyl) cyclohexane-l-caiboxylate, iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as toluene 2,6-diisocyanate), and bis-active fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene). Particularly preferred coupling agents include N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) (Carlsson et al., Biochem. J. 173:723-737 [1978]) and N-succinimidyl-4-(2-pyridylthio)pentanoate (SPP) to provide for a disulfide linkage. The linker may be attached to the maytansinoid molecule at various positions, depending on the type of the link. For example, an ester linkage may be formed by reaction with a hydroxyl group using conventional coupling techniques. The reaction may occur at the C-3 position having a hydroxyl group, the C-14 position modified with hyrdoxymethyl, the C-15 position modified with a hydroxyl group, and the C-20 position having a hydroxyl group. In a preferred embodiment, the linkage is formed at ihe C-3 position of maytansinol or a maytansinol analogue. Calicheamicin Another immunoconjugate of interest comprises an anti-TAT antibody conjugated to one or more calicheamicin molecules. The calicheamicin family of antibiotics are capable of producing double-stranded DNA breaks at sub-picomolar concentrations. For the preparation of conjugates of the calicheamicin family, see U.S. patents5,712,374,5,714,586,5,739,116,5,767,285,5,770,701,5,770,710,5,773,001,5,877,296(all to American Cyanamid Company). Structural analogues of calicheamicin which may be used include, but are not limited to, y,1, c^1, a3I, N-acetyl-yj1, PSAG and 8!j (Hinman et al., Cancer Research 53:3336-3342 (1993), Lode et al., Cancer Research 58:2925-2928 (1998) and the aforementioned U.S. patents to American Cyanamid). Another anti-tumor drug that the antibody can be conjugated is QFA which is an antifolate. Bolh calicheamicin and QFA have intracellular sites of action and do not readily cross the plasma membrane. Therefore, cellular uptake of these agents through antibody mediated internalization greatly enhances their cytotoxic effects. Other cytotoxic agents Other antitumor agents that can be conjugated to anti-TAT antibodies include BCNU, streptozoicin, vincristine and 5-fluorouracil, the family of agents known collectively LL-E33288 complex described inU.S. patents 5,053,394,5,770,710, as well as esperamicins (U.S. patent 5,877,296). 74 Enzymatically active toxins and fragments thereof which, can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordicacharantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restiictocin, phenomycin, enomycin and the tricothecenes. See, for example, WO 93/21232 published October 28,1993. Also useful is an immunoconjugate formed between an antibody and a compound with nucleolytic activity (e.g., a ribonuclease or a DNA endonuclease such as a deoxyribonuclease; DNase). For selective destruction of the tumor, the antibody may comprise a highly radioactive atom. A variety of radioactive isotopes are available for the production of radioconjugated anti-TAT antibodies. Examples include At211,1131,1125, Y90, Re186, Re188, Smls3, Bi212, P32, Pb212 and radioactive isotopes of Lu. When the conjugate is used for diagnosis, it may comprise a radioactive atom for scintigraphic studies, for example tc99m or I123, or a spin label for nuclear magnetic resonance (NMR) imaging (also known as magnetic resonance imaging, mri), such as iodine-123 again, iodine-131, indium-111, fluorine-19, carbon-13, nitrogen-15, oxygen-17, gadolinium, manganese or iron. The radio- or other labels may be incorporated in the conjugate in known ways. For example, the peptide may be biosynthesized or may be synthesized by chemical amino acid synthesis using suitable amino acid QQm 19*1 15K 1 CO precursors involving, for example, fluorine-19 inplace of hydrogen. Labels such as tc or I ,.Re ,Re and In1" can be attached via a cysteine residue in the peptide. Yttrium-90 can be attached via a lysine residue. The IODOGEN method (Fraker et al (1978) Biochem. Biophys. Res. Commun. 80:49-57 can be used to incorporate iodine-123. "Monoclonal Antibodies in Immunoscintigraphy" (Chatal,CRC Press 1989) describes other methods in detail. Conjugates of the antibody and cytotoxic agent may be made using a variety of bifunctional protein coupling agents such as N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP), succinimidyl-4-(N-maleimidomethyl) cyclohexane-l-carboxylate, iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al.. Science 238:1098 (1987). Carbon-14-labeled l-isolhiocyanatobenzyl-3-meth.yldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See W094/11026. The linker may be a "cleavable linker" facilitating release of the cytotoxic drug in the cell. For example, an acid-labile linker, peptidase-sensitive linker, photolabile linker, dimethyl linker or disulfide-containing linker (Chari et al., Cancer Research 52:127-131 (1992); U.S. Patent No. 5,208,020) may be used. Alternatively, a fusion protein comprising the anti-TAT antibody and cytotoxic agent may be made, e.g., by recombinant techniques or peptide synthesis. The length of DNA may comprise respective regions encoding 75 the two portions of the conjugate either adjacent one another or separated by a region encoding a linker peptide which does not destroy the desired properties of the conjugate. In yet another embodiment^ the antibody may be conjugated to a "receptor" (such streptavidin) for utilization in tumor pre-targeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a "ligand" 5 (e.g., avidin) which is conjugated to a cytotoxic agent (e.g., a radionucleotide). 10. Immunoliposomes The anti-TAT antibodies disclosed herein may also be formulated as immunoliposomes. A "liposome" is a small vesicle composed of various types of lipids, phospholipids and/or surfactant which is usefiil for deliveiy of a drug to a mammal. The components of the liposome are commonly arranged in a bilayer formation, similar to 10 the lipid arrangement of biological membranes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA 82:3688 (1985); Hwang et ai., Proc. Natl Acad. Sci. USA 77:4030 (1980); U.S. Pat Nos. 4,485,045 and4,544,545; and W097/38731 published October 23,1997. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 5,013,556. Particularly useful liposomes can be generated by the reverse phase evaporation method with a lipid 15 composition comprising phosphatidylcholine, cholesterol and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab' fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al., J. Biol. Chem. 257:286-288 (1982) via a disulfide interchange reaction. A chemotherapeutic agent is optionally contained within the liposome. See Gabizon et al., J. National Cancer Inst. 81(19):1484 (1989). 20 B. TAT Binding Oligopeptides TAT binding oligopeptides are oligopeptides that bind, preferably specifically, to a TAT polypeptide as described herein. TAT binding oligopeptides may be chemically synthesized using known oligopeptide synthesis methodology or may be prepared and purified using recombinant technology. TAT binding oligopeptides are usually at least about 5 amino acids in length, alternatively at least about 6,7,8,9,10, 25 11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43, 44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76, 77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99, or 100 amino acids in length ormore, wherein such oligopeptides that are capable of binding, preferably specifically, to a TAT polypeptide as described herein. TAT binding oligopeptides may be identified without undue experimentation using well known techniques. 30 In this regard, it is noted that techniques for screening oligopeptide libraries for oligopeptides that are capable of specifically binding to apolypeptide target are well known in the art(see, e.g., U.S. PatentNos. 5,556,762,5,750,373, 4,708,871,4,833,092,5^23,409,5,403,484,5,571,689,5,663,143;PCTPublica(ionNos. WO 84/03506 and W084/03564; Geysen et al., Proc. Natl. Acad. Sci. U.S.A, 81:3998-4002 (1984); Geysen et al., Proc. Natl. Acad. Sci. U.S.A., 82:178-182 (1985); Geysen etal., in SyntheticPeptides as Antigens, 130-149 (1986); Geysenetal., J. Immunol. Meth., 35 102:259-274(1987); Schoofs etal., J.Immunol., 140:611-616(1988),Cwirla,S.E.etaL(1990)Proc.Natl. Acad. Sci. USA, 87:6378;Lowman,H.B. etal. (1991)Biochemistry,30:10832; Clackson,T.etal.(1991)Nature, 352:624; Maiks, J.D. etal. (1991), J.Mol.BioL,222:581;Kang,A.S.etal.(1991)Proc.Natl. Acad. Sci. USA, 88:8363,and Smith, G. 76 P. (1991) Current Opin. Biotechnol., 2:668). Ia this regard, bacteriophage (phage) display is one well known technique which allows one to screen large oligopeptide libraries to identify members) of those libraries which are capable of specifically binding to a polypeptide target Phage display is a technique by which variant polypeptides are displayed as fusion proteins to the coat protein on the surface of bacteriophage particles (Scott, J.K. and Smith, G. P. (1990) Science 249:386). Hie utility of phage display lies in the fact that large libraries of selectively randomized protein variants (or randomly cloned cDNAs) can be rapidly and efficiently sorted for (hose sequences (hat bind to a target molecule with high affinity. Display of peptide (Cwirla, S. E. etal. (1990) Proc. Natl. Acad. Sci. USA, 87:6378) or protein (Lowman, H.B.- et al. (1991) Biochemistry, 30:10832; Oackson, T. et al. (1991) Nature, 352:624; Marks, J. D. et al. (1991), J. Mol, Biol., 222:581; Rang, AS. etal. (1991) Proc. Natl. Acad. Sci. USA, 88:8363) libraries onphagehave been used for screening millions of polypeptides or oligopeptides for ones with specific binding properties (Smith, G. P. (1991) Current Opin. Biotechnol., 2:668). Sorting phage libraries of random mutants requires a strategy for constructing and propagating a large number of variants, a procedure for affinity purification using the target receptor, and a means of evaluating the results of binding enrichments. U.S. Patent Nos. 5,223,409,5,403,484, 5,571,689, and 5,663,143. Although most phage display methods have used filamentous phage, lambdoid phage display systems (WO95/34683; U.S. 5,627,024), T4 phage display systems (Ren, Z-J. etal. (1998) Gene215:439; Zhu, Z. (1997) CAN 33:534; Jiang, J. etal. (1997) can 128:44380; Ren, Z-J. etal. (1997) CAN 127:215644; Ren, Z-J. (1996) Protein Sci. 5:1833; Efimov, V. P. et al. (1995) Virus Genes 10:173) and T7 phage display systems (Smith, G. P. and Scott, J.K. (1993) Methods in Enzymology, 217,228-257; U.S. 5,766,905) are also known. Many other improvements and variations of the basic phage display concept have now been developed. These improvements enhance the ability of display systems to screen peptide libraries for binding to selected target molecules and to display functional proteins with the potential of screening these proteins for desired properties. Combinatorial reaction devices for phage display reactions have been developed (WO 98/14277) and phage display libraries have been used to analyze and control bimolecular interactions (WO 98/20169; WO 98/20159) aiid properties of constrained helical peptides (WO 98/20036). WO 97/35196 describes a method of isolating an affinity ligand in which a phage display library is contacted with one solution in which the ligand will bind to a target molecule and a second solution in which the affinity ligand will not bind to the target molecule, to selectively isolate binding ligands. WO 97/46251 describes a method of biopanning a random phage display library with an affinity purified antibody and then isolating binding phage, followed by a micropanning process using microplate wells to isolate high affinity binding phage. The use of Staphylococcus aureus protein A as an affinity tag has also been reported (Li et al. (1998) Mol Biotech., 9:187). WO 97/47314 describes the use of substrate subtraction libraries to distinguish enzyme specificities using a combinatorial library which may be a phage display library. A method for selecting enzymes suitable for use in detergents using phage display is described in WO 97/09446. Additional methods of selecting specific binding proteins are described in U.S. Patent Nos. 5,498,538,5,432,018, and WO 98/15833. Methods of generating peptide libraries and screening these libraries are also disclosed in U.S. Patent Nos. 5,723,286,5,432,018,5,580,717,5,427,908,5,498,530,5,770,434,5,734,018,5,698,426,5,763,192, and 5,723,323. 77 C. TAT Binding Organic Molecules TAT binding organic molecules are organic molecules other than oligopeptides or antibodies as defined herein that bind, preferably specifically, to a TAT polypeptide as described herein. TAT binding organic molecules may be identified and chemically synthesized using known methodology (see, e.g., PCT PublicationNos. WO00/00823 and WOOO/39585). TAT binding oiganic molecules are usually less than about2000 daltons in size, alternatively less than about 1500,750,500,250 or 200 daltons in size, wherein such oiganic molecules that are capable of binding, preferably specifically, to a TAT polypeptide as described herein may be identified without undue experimentation using well known techniques. In this regard, it is noted that techniques for screening organic molecule libraries for molecules that are capable of binding to a polypeptide target are well known in the art (see, e.g., PCT Publication Nos. W000/00823 and WOOO/39585). TAT binding organic molecules may be, for example, aldehydes, ketones, oximes, hydrazones, semicarbazones, carbazides, primary amines, secondary amines, tertiary amines, N-substituted hydrazines, hydrazides, alcohols, ethers, thiols, thioethers, disulfides, caiboxylic acids, esters, amides, ureas, carbamates, carbonates, ketals, thioketals, acetals, thioacetals, aryl halides, aryl sulfonates, alkyl halides, alkyl sulfonates, aromatic compounds, heterocyclic compounds, anilines, alkenes, alkynes, diols, amino alcohols, oxazolidines, oxazolines, thiazolidines, thiazolines, enamines, sulfonamides, epoxides, aziridines, isocyanates, sulfonyl chlorides, diazo compounds, acid chlorides, or the like. D. Screening for Anti-TAT Antibodies. TAT Binding Oligopeptides and TAT Binding Organir. Molecules With the Desired Properties Techniques for generating antibodies, oligopeptides and oiganic molecules that bind to TAT polypeptides have been described above. One may further select antibodies, oligopeptides or other oiganic molecules with certain biological characteristics, as desired. The growth inhibitory effects of an anti-TAT antibody, oligopeptide or other organic molecule of the invention may be assessed by methods known in the art, e.g., using cells which express a TAT polypeptide either endogenously or following transfection with the TAT gene. For example, appropriate tumor cell lines and TAT-transfected cells may treated with an anti-TAT monoclonal antibody, oligopeptide or other organic molecule of tiie invention at various concentrations for a few days (e.g., 2-7) days and stained with crystal violet or MTT or analyzed by some other colorimetric assay. Another method of measuring proliferation would be by comparing 3H-thymidine uptake by the cells treated in the presence or absence an anti-TAT antibody, TAT binding oligopeptide or TAT binding oiganic molecule of the invention. After treatment, the cells are harvested and the amount of radioactivity incorporated into the DNA quantitated in a scintillation counter. Appropriate positive controls include treatment of a selected cell line with a growth inhibitory antibody known to inhibit growth of that cell line. Growth inhibition of tumor cells in vivo can be determined in various ways known in the art. Preferably, the tumor cell is one that overexpresses a TAT polypeptide. Preferably, the anti-TAT antibody, TAT binding oligopeptide or TAT binding organic molecule will inhibit cell proliferation of a TAT-expressing tumor cell in vitro or in vivo by about 25-100% compared to the untreated tumor cell, more preferably, by about 30-100%, and even more preferably by about 50-100% or 70-100%, in one embodiment, at an antibody concentration of about 0.5 to 30 (ig/ml. Growth inhibition can be measured at an antibody concentration of about 0.5 to 30 (ig/ml or about 0.5 nM to 200 nM in cell culture, where the growth inhibition is detennined 1-10 days after exposure of the tumor cells 78 to the antibody. The antibody is growth inhibitory in vivo if administration of the anti-TAT antibody at about 1 fig/kg to about 100 mg/kg body weight results in reduction in tumor size or reduction of tumor cell proliferation within about 5 days to 3 months from the first administration of the antibody, preferably within about 5 to 30 days. To select for an anti-TAT antibody, TAT binding oligopeptide or TAT binding organic molecule which induces cell death, loss of membrane integrity as indicated by, e.g., propidium iodide (PI), tiypan blue or 7AAD uptake may be assessed relative to control. A PI uptake assay can be performed in the absence of complement and immune effector cells. TAT polypeptide-expressing tumor cells are incubated with medium alone or medium containing the appropriate anti-TAT antibody (e.g, at about lO^g/ml), TAT binding oligopeptide or TAT binding organic molecule. The cells are incubated for a 3 day time period. Following each treatment, cells are washed and aliquoted into 35 mm strainer-capped 12 x 75 tubes (1ml per tube, 3 tubes per treatment group) for removal of cell clumps. Tubes then receive PI (10ng/ml). Samples may be analyzed using a FACSCAN® flow cytometer and FACSCONVERT® CellQuest software (Becton Dickinson). Those anti-TAT antibodies, TAT binding oligopeptides or TAT binding organic molecules that induce statistically significant levels of cell death as determined by PI uptake may be selected as cell death-inducing anti-TAT antibodies, TAT binding oligopeptides or TAT binding organic molecules. To screen for antibodies, oligopeptides or other organic molecules which bind to an epitope on a TAT polypeptide bound by an antibody of interest, a routine cross-blocking assay such as that described in Antibodies. A Laboratory Manual. Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed. This assay can be used to determine if a test antibody, oligopeptide or other oiganic molecule binds the same site or epitope as a known anti-TAT antibody. Alternatively, or additionally, epitope mapping can be performed by methods known in the art. For example, the antibody sequence can be mutagenized such as by alanine scanning, to identify contact residues. The mutant antibody is initailly tested for binding with polyclonal antibody to ensure proper folding. In a different method, peptides corresponding to different regions of a TAT polypeptide can be used in competition assays with the test antibodies or with a test antibody and an antibody with a characterized or known epitope. E. Antibody Dependent Enzyme Mediated Prodrug Therapy (ADEPT) The described antibodies may also be used in ADEPT by conjugating the antibody to a prodrug-activating enzyme which converts a prodrug (e.g., a peptidyl chemotherapeutic agent, see W081/01145) to an active anti-cancer drug. See, for example, WO 88/07378 and U.S. Patent No. 4,975,278. The enzyme component of the immunoconjugate useful for ADEPT includes any enzyme capable of acting on a prodrug in such a way so as to covert it into its more active, cytotoxic foim. Enzymes that are useful in the method described include, but are not limited to, alkaline phosphatase useful for converting phosphate-containing prodrugs into free drugs; arylsulfatase useful for converting sulfete-containing prodrugs into free drugs; cytosine deaminase useful for converting non-toxic 5-fluorocytosine into the anti-cancer drug, 5-fluorouracil; proteases, such as serratia protease, thermolysin, subtilisin, carboxypeptidases and cathepsins (such as cathepsins B and L), that are useful for converting peptide-containing prodrugs into free drugs; D-alanylcarboxypeptidases, useful for converting prodrugs that contain D-amino acid substituents; carbohydrate-cleaving enzymes such as P-galactosidase and neuraminidase useful for 79 converting glycosylated prodrugs into free drugs; P-lactamase useful for converting drugs derivatized with, p-lactams into free drugs; and penicillin amidases, such as penicillin V amidase or penicillia G amidase, useful for converting drugs derivatized at their amine nitrogens with phenoxyacetyl or phenylacetyl groups, respectively, into free drugs. Alternatively, antibodies with enzymatic activity, also known in the art as "abzymes", can be used to convert the prodrugs of the invention into free active drugs (see, e.g., Massey, Nature 328:457-458 (1987)). 5 Antibody-abzyme conjugates can be prepared as described herein for delivery of the abzyme to a tumor cell population. The enzymes can be covalentty bound to the anti-TAT antibodies by techniques well known in the art such as the use of the heterobifimctional crosslinking reagents discussed above. Alternatively, fusion proteins comprising at least the antigen binding region of an antibody of the invention linked to at least 10 a functionally active portion of an enzyme of the invention can be constructed using recombinant DNA techniques well known in the art (see, e.g., Neuberger et al., Nature 312:604-608 (1984). ^ F- Full-Length TAT Polypeptides Also described are newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as TAT polypeptides. In particular, cDNAs (partial and fijll-15 length) encoding various TAT polypeptides have been identified and isolated, as disclosed in further detail in ihe Examples below. As disclosed in the Examples below, various cDNA clones have been deposited with the ATCC. The actual nucleotide sequences of those clones can readily be determined by the skilled artisan by sequencing of the deposited clone using routine methods in the art. The predicted amino acid sequence can be detennined from the 20 nucleotide sequence using routine skill. For the TAT polypeptides and encoding nucleic acids described herein, in some cases, Applicants have identified what is believed to be the reading frame best identifiable with the sequence information available at the time. G. Anti-TAT Antibody and TAT Polypeptide Variants In addition to the anti-TAT antibodies and full-length native sequence TAT polypeptides described 25 herein, it is contemplated that anti-TAT antibody and TAT polypeptide variants can be prepared. Anti-TAT antibody and TAT polypeptide variants can be prepared by introducing appropriate nucleotide changes into the encoding DNA and/or by synthesis of the desired antibody or polypeptide. Those skilled in the art will appreciate that amino acid changes may alter post-translational processes of the anti-TAT antibody or TAT polypeptide, such as changing the number or position of glycosylation sites or altering the membrane anchoring characteristics. 30 Variations in the anti-TAT antibodies and TAT polypeptides described herein, can be made, for example, using any of the techniques and guidelines for conservative and non-conservative mutations set forth, for instance, in U.S. Patent No. 5,364,934. Variations may be a substitution, deletion or insertion of one or more codons encoding the antibody or polypeptide that results in a change in the amino acid sequence as compared with the native sequence antibody or polypeptide. Optionally the variation is by substitution of at least one amino 35 acid with any other amino acid in one or more of the domains of the anti-TAT antibody or TAT polypeptide. Guidance in detennining which amino acid residue may be inserted, substituted or deleted without adversely affecting the desired activity may be found by comparing the sequence of the anti-TAT antibody or TAT 80 polypqptide with that of homologous known protein molecules and minimizing the number of amino acid sequence changes made in regions of high homology. Amino acid substitutions can be the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, such as the replacement of a leucine with a serine, i.e., conservative amino acid replacements. Insertions or deletions may optionally be in the range of about 1 to 5 amino acids. The variation allowed may be determined by systematically making insertions, deletions or substitutions of amino acids in the sequence and testing the resulting variants for activity exhibited by the full-length or mature native sequence. Anti-TAT antibody and TAT polypeptide fragments are provided herein. Such fragments may be truncated at the N-terminus or C-teiminus, or may lack internal residues, for example, when compared with a full length native antibody or protein. Certain fiagments lack amino acid residues that are not essential for a desired biological activity of the anti-TAT antibody or TAT polypeptide. Anti-TAT antibody and TAT polypeptide fragments may be prepared by any of a number of conventional techniques. Desired peptide fragments may be chemically synthesized. An alternative approach involves generating antibody or polypeptide fiagments by enzymatic digestion, e.g., by treating the protein with an enzyme known to cleave proteins at sites defined by particular amino acid residues, or by digesting the DNA with suitable restriction enzymes and'isolating the desired fragment Yet another suitable technique involves isolating and amplifying a DNA fragment encoding a desired antibody or polypeptide fragment, by polymerase chain reaction (PCR). Oligonucleotides that define the desired termini of Ihe DNA fragment are employed at the 5' and 3' primers in the PCR Preferably, anti-TAT antibody and TAT polypeptide fragments share at least one biological and/or immunological activity with the native anti-TAT antibody or TAT polypeptide disclosed herein. In particular embodiments, conservative substitutions of interest are shown in Table 6 under the heading of preferred substitutions. If such substitutions result in a change in biological activity, then more substantial changes, denominated exemplary substitutions in Table 6, or as further described below in reference to amino acid classes, are introduced and the products screened. 81 Table 6 10 15 20 25 Original Exemplary Preferred Residue Substitutions Substitutions Ala (A) val; leu; ile val Arg(R) lys; gin; asn lys Asn(N) gin; his; lys; arg gin Asp(D) glu glu Cys(C) ser ser Gln(Q) asn asn Glu(E) asp " asp Gly(G) pro; ala ala His (H) asn; gin; lys; arg arg He © leu; val; met; ala; phe; norleucine leu Leu(L) norleucine; ile; val; met; ala; phe ile Lys(K) arg; gin; asn arg Met(M) leu; phe; ile leu Pho(F) leu; val; ile; ala; tyr leu Pio(P) ala ala Ser(S) (far thr Thr(T) ser ser Tq>(W) (yr;phe tyr Tyr(Y) tip; phe; thr; ser phe Val(V) ile; leu; met; phe; ala; norleucine leu Substantial modifications in function or immunological identity of the anti-TAT antibody or TAT polypeptide are accomplished by selecting substitutions Ifaat differ significantly in their effect on maintaining (a) 30 (he structure of (he polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation, (b) the charge or hydrophobicity of (he molecule at the target site, or (c) the bulk of the side chain. Naturally occurring residues are divided into groups based on common side-chain properties: (1) hydrophobic: norleucine, met, ala, val, leu, ile; (2) neutral hydrophilic: cys, ser, (fan (3) acidic: asp, glu; (4) basic: asn, gin, his, lys, arg; (5) residues that influence chain orientation: gly, pro; and (6) aromatic: trp, tyr, phe. Non-conservative substitutions will entail exchanging a member of one of these classes for another class. 40 Such substituted residues also may be introduced into (he conservative substitution sites or, more preferably, into the remaining (non-conserved) sites. The variations can be made using methods known in the art such as oligonucleotide-mediated (site-directed) mutagenesis, alanine scanning, and PCR mutagenesis. Site-directed mutagenesis [Carter et al., Nucl. Acids Res.. 13:4331 (1986); Zoller et at., Nucl. Acids Res.. 10:6487 (1987)], cassette mutagenesis PWells etal.. Gene. 45 34:315 (1985)], restrictionselectionmutagenesis [Wells etal.. Philos. Trans. R. Soc. London SerA. 317:415 (1986)] 82 or other known techniques can be performed on the cloned DNA to produce the anti-TAT antibody or TAT polypeptide variant DNA. Scanning amino acid analysis can also be employed to identify one or more amino acids along a contiguous sequence. Among the preferred scanning amino acids are relatively small, neutral amino acids. Such amino acids include alanine, glycine, serine, and cysteine. Alanine is typically a preferred scanning amino acid 5 among this group because it eliminates the side-chain beyond the beta-carbon and is less likely to alter the main-chain conformation of the variant [Cunningham and Wells, Science.244:1081-1085 (1989)]. Alanine is also typically preferred because it is the most common amino acid. Further, it is frequently found in both buried and exposed positions [Creighton, The Proteins. (W.H. Freeman & Co., N.Y.); Chothia, J. Mol. Biol.. 150:1 (1976)]. If alanine substitution does not yield adequate amounts of variant, an isoteric amino acid can be used. 10 Any cysteine residue not involved in maintaining the proper conformation of the anti-TAT antibody or TAT polypeptide also may be substituted, generally with serine, to improve the oxidative stability of the molecule and prevent aberrant crosslinking. Conversely, cysteine bond(s) may be added to the anti-TAT antibody or TAT polypqptide to improve its stability (particulariy where the antibody is an antibody fragment such as an Fv fragment). 15 A particularly preferred type of substitutional variant involves substituting one or more hypervariable region residues of a parent antibody (e.g., a humanized or human antibody). Generally, the resulting variants) selected for further development will have improved biological properties relative to the parent antibody from which they are generated. A convenient way for generating such substitutional variants involves affinity maturation using phage display. Briefly, several hypervariable region sites (e.g., 6-7 sites) are mutated to generate 20 all possible amino substitutions at each site. The antibody variants thus generated are displayed in a monovalent fashion from filamentous phage particles as fusions to the gene in product of M13 packaged within each particle. The phage-displayed variants are then screened for their biological activity (e.g., binding affinity) as herein disclosed. In order to identify candidate hypervariable region sites for modification, alanine scanning mutagenesis can be performed to identify hypervariable region residues contributing significantly to antigen binding. 25 Alternatively, or additionally, it may be beneficial to analyze a crystal structure of the antigen-antibody complex to identify contact points between the antibody and human TAT polypqptide. Such contact residues and neighboring residues are candidates for substitution according to the techniques elaborated herein. Once such variants are generated, the panel of variants is subjected to screening as described herein and antibodies with superior properties in one or more relevant assays may be selected for fitrfher development. 30 Nucleic acid molecules encoding amino acid sequence variants of the anti-TAT antibody are prepared by a variety of methods known in the art These methods include, but are not limited to, isolation from a natural source (in the case of naturally occurring amino acid sequence variants) or preparation by oligonucleotide-mediated (or site-directed) mutagenesis, PCR mutagenesis, and cassette mutagenesis of an earlier prepared variant or a non-variant version of the anti-TAT antibody. 35 H. Modifications of Anti-TAT Antibodies and TAT Polypeptides Covalent modifications of anti-TAT antibodies and TAT polypeptides are also described. One type of covalent modification includes reacting targeted amino acid residues of an anti-TAT 83 antibody or TAT polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C- terminal residues of the anti-TAT antibody or TAT polypqptide. Derivatization with bifunctional agents is useful, for instance, for crosslinking anti-TAT antibody or TAT polypeptide to a water-insoluble support matrix or surface for use in the method for purifying anti-TAT antibodies, and vice-versa. Commonly used crosslinking agents include, e.g., 1,1 -bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinitnide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-maleimido-l,8-octane and agents such as methyl-3-[(p-azidophenyl)dithio]propioimidate. Other modifications include deamidation of ghitaminyl and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seiyl or threonyl residues, methylation of the a-amino groups of lysine, arginine, and histidine side chains [T.E. Creighton, Proteins: Sfaucture and Molecular Properties. W.H. Freeman & Co., SanFrancisco, pp. 79-86 (1983)], acetylation of the N-teiminal amine, and amidation of any C-terminal carboxyl group. Another type of covalent modification of the anti-TAT antibody or TAT polypeptide described comprises altering the native glycosylation pattern of the antibody or polypeptide. "Altering the native glycosylation pattern" is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence anti-TAT antibody or TAT polypeptide (either by removing the underlying glycosylation site or by deleting the glycosylation by chemical and/or enzymatic means), and/or adding one or more glycosylation sites that are not present in the native sequence anti-TAT antibody or TAT polypeptide. In addition, the phrase includes qualitative changes in the glycosylation of the native proteins, involving a change in the nature and proportions of the various carbohydrate moieties present Glycosylation of antibodies and other polypeptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate moiety to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the caibohydrate moiety to the asparagine side chain. Thus, the presence of either of these tripeptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of one of the sugars N-aceylgalactosamine, galactose, or xylose to ahydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used. Addition of glycosylation sites to the anti-TAT antibody or TAT polypeptide is conveniently accomplished by altering the amino acid sequence such that it contains one or more of the above-described tripeptide sequences (for N-linked glycosylation sites). The alteration may also be made by the addition of, or substitution by, one or more serine or threonine residues to the sequence of the original anti-TAT antibody or TAT polypeptide (for O-linked glycosylation sites). The anti-TAT antibody or TAT polypeptide amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the anti-TAT antibody or TAT polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids. 84 Another means of increasing the number of carbohydrate moieties on the anti-TAT antibody or TAT polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, e.g., in WO 87/05330 published 11 September 1987, and in Aolinand Wriston. CRC Crit. Rev. Biochem.. pp. 259-306 (1981). Removal of carbohydrate moieties present on the anti-TAT antibody or TAT polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosyiation techniques are known in the art and described, for instance, by Hakimuddin, et al., Arch. Biochem. Biophvs.. 259:52 (1987) and by Edge et al., Anal. Biochem.. 118:131 (1981). Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo- and exo-glycosidases as described by Thotakura et al., Meth. Enzvmol.. 138:350 (1987). Another type of covalent modification of anti-TAT antibody or TAT polypeptide comprises linking the antibody or polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S. Patent Nos. 4,640,835; 4,496,689; 4,301,144;4,670,417; 4,791,192or4,179,337. The antibody orpolypeptide also may be entrapped mroicrocapsules prepared, for example, by coacervation techniques or by interfacial polymerization (for example, hydroxymetbylcellulose or gelatin-microcapsules and poly-(methyImethacylate) microcapsules, respectively), in colloidal drugdelivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules), or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences. 16th edition, Oslo, A., Ed., (1980). The anti-TAT antibody or TAT polypeptide described may also be modified in a way to form chimeric molecules comprising an anti-TAT antibody or TAT polypeptide fused to another, heterologous polypeptide or amino acid sequence. La one embodiment, such a chimeric molecule comprises a fusion of the anti-TAT antibody or TAT polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind. The epitope tag is generally placed at the amino- or carboxyl- terminus of the anti-TAT antibody or TAT polypeptide. The presence of such epitope-tagged forms of the anti-TAT antibody or TAT polypeptide can be detected using an antibody against the tag polypeptide. Also, provision of the epitope tag enables the anti-TAT antibody or TAT polypeptide to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag. Various tag polypeptides and their respective antibodies are well known in the art. Examples include poly-histidine (poly-his) orpoly-histidine-glycine (poly-his-gly) tags; the fluHA tag polypeptide andits antibody 12CA5 [Field et al., Mol. Cell. Biol.. 8:2159-2165 (1988)]; thec-myctagand the 8F9,3C7,6E10, G4, B7 and 9E10 antibodies thereto [Evan et al., Molecular and Cellular Biology. 5:3610-3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody [Paborsky et al., Protein Engineering. 3(6):547-553 (1990)]. Other tag polypeptides include the Flag-peptide [Hopp et al., BioTechnologv. £1204-1210 (1988)]; the KT3 epitope peptide [Martin et al., Science. 255:192-194 (1992)]; an a-tubulin epitope peptide [Skinner et al., J. Biol. Chan.. 266:15163-15166 (1991)]; and the T7 gene 10 protein peptide tag [Lutz-Freyermuth et al., Proc. Natl. Acad. Soi. USA. 87:6393-6397 (1990)]. 85 In aa alternative embodiment, the chimeric molecule may comprise a fusion of the anti-TAT antibody or TAT polypqptide with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule (also referred to as an "immunoadhesin"), such a fusion could be to the Fc region of an IgG molecule. The Ig fusions preferably include the substitution of a soluble (transmembrane domain deleted or inactivated) form of an anti-TAT antibody or TAT polypeptide in place of at least one variable region within an 5 Ig molecule. In a particularly preferred embodiment, the immunoglobulin fusion includes the hinge, CBDj and CHj, or tiie hinge, CH„ CHj and CH3 regions of an IgGl molecule. For the production of immunoglobulin fusions see also US Patent No. 5,428,130 issued June 27,1995. L Preparation of Anti-TAT Antibodies and TAT Polypeptides The description below relates primarily to production of anti-TAT antibodies and TAT polypeptides by 10 culturing cells transformed or transacted with a vector containing anti-TAT antibody- and TAT polypeptide-encoding nucleic acid. It is, of course, contemplated that alternative methods, which are well known in the art, may be employed to prepare anti-TAT antibodies and TAT polypeptides. For instance, the appropriate amino acid sequence, or portions thereof, may be produced by direct peptide synthesis using solid-phase techniques [see, e.g., Stewart et aL, Solid-Phase Peptide Synthesis. Wit Freeman Co., San Francisco, CA (1969); Memfield, J.Am. 15 Chem. Soc.. 85:2149-2154 (1963)]. In vitro protein synthesis may be performed using manual techniques or by automation. Automated synthesis may be accomplished, for instance, using an Applied Biosystems Peptide Synthesizer (Foster City, CA) using manufacturer's instructions. Various portions of the anti-TAT antibody or TAT polypeptide may be chemically synthesized separately and combined using chemical or enzymatic methods to produce the desired anti-TAT antibody or TAT polypeptide. 20 1. Isolation of DNA Encoding Anti-TAT Antibody or TAT Polypeptide DNA encoding anti-TAT antibody or TAT polypeptide may be obtained from a cDNA library prepared from tissue believed to possess the anti-TAT antibody or TAT polypeptide mRNA and to express it at a detectable level. Accordingly, human anti-TAT antibody or TAT polypeptide DNA can be conveniently obtained from a cDNA library prepared from human tissue. The anti-TAT antibody- or TAT polypeptide-encoding gene may also 25 be obtained from a genomic library or by known synthetic procedures (e.g., automated nucleic acid synthesis). libraries can be screened with probes (such as oligonucleotides of at least about 20-80 bases) designed to identify the gene of interest or the protein encoded by it. Screening the cDNA or genomic library with the selected probe may be conducted using standard procedures, such as described in Sambrook et al., Molecular ("Honing: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989). An alternative means to 30 isolate the gene encoding anti-TAT antibody or TAT polypqptide is to use PCR methodology [Sambrook et aL, suora: Dieffenbach et al., PCR Primer: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 1995)]. Techniques for screening a cDNA library are well known in the art The oligonucleotide sequences selected as probes should be of sufficient length and sufficiently unambiguous that false positives are minimized. The oligonucleotide is preferably labeled such that it can be detected upon hybridization to DNA in the libraiy 35 being screened. Methods of labeling are well known in the art, and include the use of radiolabels like 3iP-labeled ATP, biotinylation or enzyme labeling. Hybridization conditions, including moderate stringency and high stringency, are provided in Sambrook et al., supra. 86 Sequences identified in such library screening methods can be compared and aligned to other known sequences deposited and available in public databases such as GenBank or other private sequence databases. Sequence identity (at either the amino acid or nucleotide level) within defined regions of the molecule or across the full-length sequence can be determined using methods known in the art and as described herein. Nucleic acid having protein coding sequence may be obtained by screening selected cDNA or genomic libraries using the deduced amino acid sequence disclosed herein for the first time, and, if necessary, using conventional primer extension procedures as described in Sambrook et al., supra, to detect precursors and processing intermediates of mRNA that may not have been reverse-transcribed into cDNA. - -2. Selection and Transformation of Host Cells Host cells are transfected or transformed with expression or cloning vectors described herein for anti-TAT antibody or TAT polypeptide production and cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying the genes encoding the desired sequences. The culture conditions, such as media, temperature, pH and the like, can be selected by the skilled artisan without undue experimentation. In general, principles, protocols, and practical techniques for maximizing the productivity of cell cultures can be found in Mammalian Cell Biotechnology: a Practical Approach. M. Butler, ed. (ERL Press, 1991) and Sambrook et al., supra. Methods of eukaryotic cell transaction and prokaiyotic cell transformation are known to the ordinarily skilled artisan, for example, CaClj, CaP04, liposome-mediated and electroporation. Depending on the host cell used, transformation is performed using standard techniques appropriate to such cells. The calcium treatment employing calcium chloride, as described in Sambrook et al., supra, or electroporation is generally used for prokaryotes. Infection with Agrobacterium tumefaciens is used for transformation of certain plant cells, as described by Shaw etal.. Gene. 23:315 (1983) and WO 89/05859 published 29 June 1989. Formammalian cells without such cell walls, the calcium phosphate precipitation method of Graham mid van der Eb, Virology. 52:456-457 (1978) can be employed. General aspects of mammalian cell host system transfections have been described in U.S. Patent No. 4,399,216. Transformations into yeast are typically carried out according to the method of Van Solingen et al., J. Bact„ 130:946 (1977) and Hsiao et al., Proc. Natl. Acad Sci. (USA1.76:3829 (1979). However, other methods for introducing DNA into cells, such as by nuclear microinjection, electroporation, bacterial protoplast fusion with intact cells, or polycations, e.g., polybrene, polyornithine, may also be used. For various techniques for transforming mammalian cells, see Keown et al.. Methods in Enzvmology. 185:527-537 (1990) and Mansour etal., Nature. 336:348-352 (19881. Suitable host cells for cloning or expressing the DNA in Ihe vectors herein include prokaryote, yeast, or higher eukaiyote cells. Suitable prokaryotes include but are not limited to eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as E. coli. Various E. coli strains are publicly available, such as E. coli K12 strain MM294 (ATCC 31,446); E. coli X1776 (ATCC 31,537); E. coli strain W3110 (ATCC 27,325) and K5 772 (ATCC 53,635). Other suitable prokaiyotic host cells include Enterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacilli such as B. subttlis and B. licheniformis (e.g., B. licheniformis 41P disclosed in DD 266,710 published 12 April 1989), Pseudomonas such as 87 P. aeruginosa, and Streptomyces. These examples are illustrative rather than limiting. Strain W3110 is one particularly preferred host or parent host because it is a common host strain for recombinant DNA product fermentations. Preferably, the host cell secretes minimal, amounts of proteolytic enzymes. For example, strain W3110 may be modified to effect a genetic mutation in the genes encoding proteins endogenous to the host, with examples of such hosts including E. coli W3110 strain 1A2, which has the complete genotype tonA; E. coli W3110 strain 9E4, which has the complete genotype tonA ptr3; E. coli W3110 strain 27C7 (ATCC 55,244), which has the complete genotype tonA ptr3 phoA El5 (argF-lac)169 degP ompTkatf; E. coli W3110 strain 37D6, which has the complete genotype toiiA ptrSphoA E15 (argF-lac)169 degP ompT rbs7 ilvG kanr\ E. coli W3110 strain 40B4, which is strain 37D6 with a non-kanamycin resistant degP deletion mutation; and an K coli strain having mutant periplasmic protease disclosed inU.S. Patent No. 4,946,783 issued 7 August 1990. Alternatively, in vitro methods of cloning, e.g., PCR or other nucleic acid polymerase reactions, are suitable. Full length antibody, antibody fragments, and antibody fusion proteins can be produced in bacteria, in particular when glycosylation and Fc effector function are not needed, such as when the therapeutic antibody is conjugated to a cytotoxic agent (e.g., a toxin) and Ihe immunoconjugate by itself shows effectiveness in tumor cell destruction. Full length antibodies have greater half life in circulation. Production in E. coli is faster and more cost efficient For expression of antibody fragments and polypeptides in bacteria, see, e.g., U.S. 5,648,237 (Carter et al.),U.S. 5,789,199 (My etal.), andU.S. 5,840,523 (Simmons et al.) whichdescribes translationinitiationregio (TER.) and signal sequences for optimizing expression and secretion, these patents incorporated herein by reference. After expression, the antibody is isolated from the E. coli cell paste in a soluble fraction and can be purified through, e.g., a protein A or G column depending on the isotype. Final purification can be carried out similar to the process for purifying antibody expressed e.g„ in CHO cells. In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for anti-TAT antibody- or TAT polypeptide-encoding vectors. Saccharomyces cerevisiae is a commonly used lower eukaryotic host microorganism. Others include Schizosaccharomyces pombe (Beach and Nurse, Nature. 290:140 [1981]; EP 139,383 published 2 May 1985); Kluyveromyces hosts (U.S. Patent No. 4,943,529; Fleer et al., Bio/Technology. 9:968-975 (1991)) such as, e.g, K. lactis (MW98-8C, CBS683, CBS4574; Louvencourt et al., T. Bacteriol.. 154(2):737-742[1983]),.K fragilis (ATCC 12,424), K bulgaricus (ATCC 16,045), K. mckeramii (ATCC 24,178), K. waltii (ATCC 56,500), K drosophilarum (ATCC 36,906; Van den Berg et al., Bio/Technology. 8:135 (1990)), K. thermotolerans, andiC marxianus;yarrowia (EP 402,226); Pichiapastoris (EP 183,070; Sreekrishna et al., J. Basic Microbiol.. 28:265-278 [1988]); Candida; Trichoderma reesia (EP 244,234); Neurospora crassa (Case et al., Proc. Natl. Acad. Sci. USA. 76:5259-5263 [1979]); Schwanniomyces such as Schwanniomyces occidentalis (EP 394,538 published 31 October 1990); and filamentous fungi such as, e.g., Neurospora, Penicillium, Tolypocladitm (WO 91/00357 published 10 January 1991), and Aspergillus hosts such as ■^.Hid«&HMfflallanoeetal..Biochem.BioDhvs. Res. Commun.. 112:284-289 ri9831:TilburnetaLGene. 26:205-221 ri9831: Yelton et al.. Proc. Natl. Acad. Sci. USA. 81:1470-1474 [1984]) and A niger (Kelly and Hynes, EMBO J„ 4:475-479 [1985]). Methylotropic yeasts are suitable herein and include, but ate not limited to, yeast capable of growth on methanol selected from the genera consisting of Hansenula, Candida, Kbeckera, Pichia, Saccharomyces, Torulopsis, and Rhodotorula. A list of specific species that are exemplary of this class of yeasts 88 may be found in C. Anthony, The Biochemistry of Methvlotrophs. 269 (1982). Suitable host cells for the expression of glycosylated anti-TAT antibody or TAT polypeptide ate derived from multicellular organisms. Examples of invertebrate cells include insect cells such as Drosophila S2 and Spodoptera Sf9, as well as plant cells, such as cell cultures of cotton, corn, potato, soybean, petunia, tomato, and tobacco. Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts such as Spodoptera frugiperda (caterpillar), Aedes aegypti (mosquito), Aedes albopictus (mosquito), Drosophila melanogaster (fruitfly), and Bombyx mori have been identified. A variety of viral strains for transfection are publicly available, e.g., the L-l variant ofAutographa californiea NPV and the Bm-5 strain of Bombyx mori NPV, and such viruses may be used as the virus herein, particularly for transfection of Spodoptera frugiperda cells. However, interest has been greatest in vertebrate cells, and propagation of vertebrate cells in culture (tissue culture) has become a routine procedure. Examples of usefiil mammalian host cell lines are monkey kidney CV1 linetransformedby SV40 (COS-7, ATCC CRL1651); human embiyonic kidney line (293 or293 cells subcloned for growthin suspension culture, Graham etal.. J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK, ATCC CCL10~>: Chinese hamster ovarv cells/-DHFR CCHO. Urlaub et al.. Proc. Natl. Acad. Sci. USA77:4216 C1980Y): mouse Sertoli cells (IM4, Mather, Biol. Reorod. 23:243-251 (1980)); monkey kidney cells (CV1 ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL-1587); human cervical carcinoma cells (HELA, ATCC CCL 2); canine kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3 A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, HB 8065); mouse mammaiy tumor (MMT060562, ATCC CCL51); TRI cells (Mather et al., Annals N.Y. Acad. Sci. 383:44-68 (1982)); MRC 5 cells; FS4 cells; and a human hepatoma line (Hep G2). Host cells are transformed with the above-described expression or cloning vectors for anti-TAT antibody or TAT polypeptide production and cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying the genes encoding the desired sequences. 3. Selection and Use of a Replioable Vector The nucleic acid (e.g., cDNA or genomic DNA) encoding anti-TAT antibody or TAT polypeptide may be inserted into a replicable vector for cloning (amplification of the DNA) or for expression. Various vectors are publicly available. Ihe vector may, for example, be in the form of a plasmid, cosmid, viral particle, or phage. The appropriate nucleic acid sequence may be inserted into the vector by a variety of procedures. In general, DNA is inserted into an appropriate restriction endonuclease site(s) using techniques known in the art. Vector components generally include, but are not limited to, one or more ofa signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence. Construction of suitable vectors containing one or more of these components employs standard ligation techniques which are known to the skilled artisan. The TAT may be produced recombinantly not only directly, but also as a fusion polypeptide with a heterologous polypeptide, which may be a signal sequence or other polypeptide having a specific cleavage site at the N-terminus of the mature protein or polypqptide. In general, the signal sequence may be a component of tiie vector, or it may be a part of the anti-TAT antibody- or TAT polypeptide-encoding DNA that is inserted into 89 the vector. The signal sequence may be a prokaiyotic signal sequence selected, for example, from the group of the alkaline phosphatase, penicillinase, lpp, or heat-stable enterotoxin II leaders. For yeast secretion the signal sequence may be, e.g., the yeast invertase leader, alpha fector leader (including Saccharomyces and KLuyveromyces a-fector leaders, the latter described in U.S. Patent No. 5,010,182), or acid phosphatase leader, the C. albicans glucoatnylase leader (EP 362,179 published 4 April 1990), or the signal described in WO 90/13646 published 15 November 1990. In mammalian cell expression, mammalian signal sequences may be used to direct secretion of the protein, such as signal sequences from secreted polypeptides of the same or related species, as well as viral secretory leaders. - Both expression and cloning vectors contain a nucleic acid sequence that enables the vector to replicate in one or more selected host cells. Such sequences are well known for a variety of bacteria, yeast, and viruses. The origin of replication from the plasmid pBR322 is suitable for most Gram-negative bacteria, the 2^ plasmid origin is suitable for yeast, and various viral origins (SV40, polyoma, adenovirus, VSV or BPV) are useful for cloning vectors in mammalian cells. Expression and cloning vectors will typically contain a selection gene, also termed a selectable marker. Typical selection genes encode proteins that (a) confer resistance to antibiotics or other toxins, e.g., ampicillin, neomycin, methotrexate, or tetracycline, (b) complement auxotrophic deficiencies, or (c) supply critical nutrients not available from complex media, e.g., the gene encoding D-alanine racemase for Bacilli. An example of suitable selectable markers for mammalian cells are those that enable the identification of cells competent to take up the anti-TAT antibody- or TAT polypeptide-encoding nucleic acid, such as DHFR or thymidine kinase. An appropriate host cell when wild-type DHFR is employed is the CHO cell line deficient in DHFR activity, prepared and propagated as described bvUrlaub etal.. Proc. Natl. Acad. Sci. USA. 77:4216(1980"). A suitable selection gene for use in yeast is the tipl gene present in the yeast plasmid YRp7 [Stinchcomb et al., Nature. 282:39 (1979); Kingsman et aL, Gene. 7:141 (1979); Tschemper et al., Gene. 10:157 (1980)]. The trpl gene provides a selection marker for a mutant strain of yeast lacking the ability to grow in tryptophan, for example, ATCC No. 44076 or PEP4-1 [Jones, Genetics. 85:12 (1977)]. Expression and cloning vectors usually contain a promoter operably linked to the anti-TAT antibody-or TAT polypeptide-encoding nucleic acid sequence to direct mRNA synthesis. Promoters recognized by a variety of potential host cells are well known. Promoters suitable for use with prokatyotic hosts include the p-lactamase and lactosepromoter systems [Chang etal.,Nature, 275:615 (1978); Goeddel et al., Nature. 281:544 (1979)], alkaline phosphatase, a tryptophan (trp) promoter system [Goeddel, Nucleic Acids Res.. 8:4057 (1980); EP 36,776], and hybrid promoters such as the tac promoter [deBoer et aL, Proc. Natl. Acad. Sci. USA. 80:21-25 (1983)]. Promoters for use in bacterial systems also will contain a Shine-Dalgarno (S.D.) sequence operably linked to the DNA encoding anti-TAT antibody or TAT polypeptide. Examples of suitable promoting sequences for use with yeast hosts include the promoters for 3-phosphoglycerate kinase IHitzettian et al.. J. Biol. Chem.. 255:2073 (1980)] orother glycolytic enzymes [Hess etal., J. Adv. Enzvme Reg.. 7:149 (1968); Holland, Biochemistry. 17:4900 (1978)], such as enolase, glyceraldehyde-3-phosphate dehydrogenase, hexokinase, pyruvate decarboxylase, phosphofructokinase, glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triosephosphate isomerase, phosphoglucose isomerase, 90 and glucokinase. Other yeast promoters, which axe inducible promoters having the additional advantage of transcription controlled by growth conditions, ate the promoter regions for alcohol dehydrogenase 2, isocytochrome C, acid phosphatase, degradative enzymes associated with nitrogen metabolism, metallothionein, glyceraldehyde-3-phosphate dehydrogenase, and enzymes responsible for maltose and galactose utilization. Suitable vectors and 5 promoters for use in yeast expression are further described in EP 73,657. Anti-TAT antibody or TAT polypeptide transcription from vectors in mammalian host cells is controlled, for example;'by promoters obtained from Ihe genomes of viruses such as polyoma virus, fowlpox virus (UK 2,211,504 published 5 My 1989), adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus 40 (SV40), from heterologous mammalian 10 promoters, e.g., the actin promoter or an immunoglobulin promoter, and from heat-shock promoters, provided such promoters are compatible with the host cell systems. . Transcription of a DNA encoding the anti-TAT antibody or TAT polypeptide by higher eukaiyotes may be increased by inserting an enhancer sequence into the vector. Enhancers are cis-acting elements of DNA, usually about from 10 to 300 bp, that act on a promoter to increase its transcription. Many enhancer sequences 15 are now known from mammalian genes (globin, elastase, albumin, a-fetoprotein, and insulin). Typically, however, one will use an enhancer from a eukaryotic cell virus. Examples include the SV40 enhancer on the late side of the replication origin (bp 100-270), the cytomegalovirus early promoter enhancer, die polyoma enhancer on the late side of the replication origin, and adenovirus enhancers. The enhancer may be spliced into the vector at a position 5' or 3' to the anti-TAT antibody or TAT polypeptide coding sequence, but is preferably located at a site 5' from 20 the promoter. Expression vectors used in eukaryotic host cells (yeast, fungi, insect, plant, animal, human, or nucleated cells from other multicellular organisms) will also contain sequences necessary for the termination of transcription and for stabilizing the mRNA. Such sequences are commonly available from the 5' and, occasionally 3', untranslated regions of eukaryotic or viral DNAs or cDNAs. These regions contain nucleotide segments 25 transcribed as polyadenylated fragments in the untranslated portion of the mRNA encoding anti-TAT antibody or TAT polypeptide. Still other methods, vectors, and host cells suitable for adaptation to the synthesis of anti-TAT antibody or TAT polypeptide in recombinant vertebrate cell culture are described in Gething et al., Nature. 293:620-625 (1981V Mantei et al.. Nature. 281:40-46 (19791: EP 117.060: and EP 117,058. 30 4. Culturing the Host Cells The host cells used to produce Ihe anti-TAT antibody or TAT polypeptide of this invention may be cultured in a variety of media. Commercially available media such as Ham's F10 (Sigma), Minimal Essential Medium ((MEM), (Sigma), RPMI-1640 (Sigma), and Dulbecco's Modified Eagle's Medium ((DMEM), Sigma) are suitable for culturing the host cells. In addition, any of the media described in Ham et al., Meth. Bnz. 58:44 (1979), Barnes et 35 al., Anal. Biochem.lQ2:255 (1980), U.S. Pat. Nos. 4,767,704; 4,657,866; 4,927,762; 4,560,655; or 5,122,469; WO 90/03430; WO 87/00195; or U.S. Patent Re. 30,985 may be used as culture media for tire host cells. Any of these media may be supplemented as necessary with hormones and/or other growth factors (such as insulin, transferrin, 91 or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics (such as GENTAMYCIN™ drug), trace elements (defined as inorganic compounds usually present at final concentrations in Ihe micromolarrange), and glucose or an equivalent energy source. Any other necessary supplements may also be included at appropriate concentrations that would be known to those skilled in the art The culture conditions, such as temperature, pH, and die like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan. 5. Detecting Gene Amplification/Expression Gene amplification and/or expression may be measured in a sample directly, for example, by conventional Southern blotting, Northern blotting to quantitate the transcription of mRNA [Thomas, Proc. Natl. Acad. Sci. USA. 77:5201-5205 (1980)], dot blotting (DNA analysis), or in situ hybridization, using an appropriately labeled probe, based on the sequences provided herein. Alternatively, antibodies may be employed that can recognize specific duplexes, including DNA duplexes, ENA duplexes, andDNA-KNAhybrid duplexes or DNA-protein duplexes. The antibodies in turn may be labeled and the assay may be carried out where the duplex is bound to a surface, so that upon the formation of duplex on the surfece, the presence of antibody bound to the duplex can be detected. Gene expression, alternatively, may be measured by immunological methods, such as immunohistochemical staining of cells or tissue sections and assay of cell culture or body fluids, to quantitate directly the expression of gene product Antibodies usefiil for immunohistochemical staining and/or assay of sample Quids may be either monoclonal or polyclonal, and may be prepared in any mammal. Conveniently, the antibodies may be prepared against a native sequence TAT polypeptide or against a synthetic peptide based on the DNA sequences provided herein or against exogenous sequence fused to TAT DNA and encoding a specific antibody epitope. 6. Purification of Anti-TAT Antibody and TAT Polypeptide Forms of anti-TAT antibody and TAT polypeptide may be recovered from culture medium or from host cell lysates. If membrane-bound, it can be released from the membrane using a suitable detergent solution (e.g. Triton-X 100) or by enzymatic cleavage. Cells employed in expression of anti-TAT antibody and TAT polypeptide can be disrupted by various physical or chemical means, such as freeze-thaw cycling, sonication, mechanical disruption, or cell lysing agents. It may be desired to purify anti-TAT antibody and TAT polypeptide from recombinant cell proteins or polypeptides. The following procedures are exemplary of suitable purification procedures: by fractionation on an ion-exchange column; ethanol precipitation; reverse phase HPLC; chromatography on silica or on a cation-exchange resin such as DEAE; chromatofocusing; SDS-PAGE; ammonium sulfate precipitation; gel filtration using, for example, Sephadex G-75; protein A Sepharose columns to remove contaminants such as IgG; and metal chelating columns to bind epitope-tagged forms of the anti-TAT antibody and TAT polypeptide. Various methods of protein purification may be employed and such methods are known in the art and described for example in Deutscher, Methods in Enzvmologv. 182 (1990); Scopes, Protein Purification: Principles and Practice. Springer-Veriag, New York(1982). The purification step(s) selected will depend, for example, on the nature of the production process used and the particular anti-TAT antibody or TAT polypeptide produced. 92 When using recombinant techniques, the antibody can be produced intracellular^, in the periplasmic space, or directly secreted into the medium. If the antibody is produced intracellular^/, as a first step, the particulate debris, either host cells or lysed fragments, are removed, for example, by centrifugation or ultrafiltration. Carter et al., Bio/Technology 10:163-167 (1992) describe a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli. Briefly, cell paste is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF) over about 30 min. Cell debris can be removed by centrifugation. Where the antibody is secreted into the medium, supematants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit A protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants. The antibody composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being the preferred purification technique. The suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain that is present in the antibody. Protein A can be used to purify antibodies that are based on human yl, y2 or y4 heavy chains (Lindmark et a!., J. Immunol. Meifa. 62:1-13 (1983)). Protein G is recommended for all mouse isotypes and for human y 3 (Guss et al..EMBO J. 5:15671575 (1986)). The matrix to which the affinity ligand is attached is most often agarose, but other matrices are available. Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzeae allow for faster flow rates and shorter processing times than can be achieved with agarose. Where the antibody comprises a C^ domain, the Bakeibond ABX™resin (J. T. Baker, Phillipsburg, NJ) is useful for purification. Other techniques for protein purification such as fractionation on an ion-exchange column, ethanol precipitation, Reverse Phase HPLC, chromatography on silica, chromatography on heparin SEPHAROSE™ chromatography on an anion or cation exchange resin (such as a polyaspartic acid column), chromatofocusing, SDS-PAGE, and ammonium sulfate precipitation are also available depending on the antibody to be recovered. Following any preliminary purification step(s), the mixture comprising the antibody of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH between about 2.5-4.5, preferably performed at low salt concentrations (e.g., from about 0-0.25M salt). J. Pharmaceutical Formulations Therapeutic formulations of the anti-TAT antibodies, TAT binding oligopeptides, TAT binding organic molecules and/or TAT polypeptides usefiil as described herein are prepared for storage by mixing the antibody, polypeptide, oligopeptide or organic molecule having the desired degree of purity with optional pharmaceutical acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as acetate, Tris, phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or betuyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than 93 about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; tonicifiers such as trehalose and sodium chloride; sugars such as sucrose, manoitol, trehalose or sorbitol; surfactant such as polysorbate; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and/or non-ionic surfactants such as TWEEN®, PLURONICS® or polyethylene glycol (PEG). The antibody preferably comprises the antibody at a concentration of between 5-200 mg/ml, preferably between 10-100 mg/ml. - ... . The formulations herein may also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. For example, in addition to an anti-TAT antibody, TAT binding oligopeptide, or TAT binding organic molecule, it may be desirable to include in the one fonnulation, an additional antibody, e.g., a second anti-TAT antibody which binds a different epitope on the TAT polypeptide, or an antibody to some other taiget such as a growth factor tirat affects the growth of the particular cancer. Alternatively, or additionally, the composition may further comprise a chemotherapeutic agent, cytotoxic agent, cytokine, growth inhibitoiy agent, anti-hormonal agent, and/or cardioprotectant Such molecules are suitably present in combination in amounts that are effective for the purpose intended. The active ingredients may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poiy-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences. 16th edition, Osol, A. Ed. (1980). Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations include semi-permeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methaciylate), or poly(vinyla!cohol)), polylactides (U.S. Pat No. 3,773,919), copolymers of L-glutamic acid and y ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT® (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid. The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes. K. Diagnosis and Treatment with Anti-TAT Antibodies. TAT Binding Oligopeptides and TAT Binding Organic Molecules To determine TAT expression in the cancer, various diagnostic assays are available, hi one embodiment, TAT polypeptide overexpression may be analyzed by immunohistochemistay (IHC). Parrafin embedded tissue sections from a tumor biopsy may be subjected to the IHC assay and accorded a TAT protein staining intensity criteria as follows: 94 Score 0-no staining is observed or membrane staining is observed in less than 10% of tumor cells. Score 1+ - a faint/barely perceptible membrane staining is detected in more than 10% of the tumor cells. The cells are only stained in part of their membrane. Score 24- - a weak to moderate complete membrane staining is observed in more than 10% of the tumor cells. Score 3+ - a moderate to strong complete membrane staining is observed in more ihan 10% of the tumor cells. Those tumors with O or 1+" scores for TAT polypeptide expression may be characterized-as not overexpressing TAT, whereas those tumors with 2+ or 3+ scores may be characterized as overexpressing TAT. Alternatively, or additionally, FISH assays such as the INFORM® (sold by Ventana, Arizona) or PATHVISION® (Vysis, Illinois) maybe carried out onformalin-fixed, paraffin-embedded tumor tissue to determine the extent (if any) of TAT overexpression in the tumor. TAT overexpression or amplification may be evaluated using an in vivo diagnostic assay, e.g., by administering a molecule (such as an antibody, oligopeptide or oiganic molecule) which binds the molecule to be detected and is tagged with a detectable label (e.g., a radioactive isotope or a fluorescent label) and externally scanning the patient for localization of the label. As described above, the anti-TAT antibodies, oligopeptides and organic molecules of the invention have various non-therapeutic applications. The anti-TAT antibodies, oligopeptides and organic molecules of the present invention can be useful for diagnosis and staging of TAT polypeptide-expressing cancers (e.g., in radioimaging). The antibodies, oligopeptides and organic molecules are also useful for purification or I immunoprecipitation of TAT polypeptide from cells, for detection and quantitation of TAT polypeptide in vitro, e.g., in an ELISA or a Western blot, to kill and eliminate TAT-expressing cells from a population of mixed cells as a step in the purification of other cells. Currently, depending on the stage of the cancer, cancer treatment involves one or a combination of the following therapies: surgery to remove the cancerous tissue, radiation therapy, and chemotherapy. Anti-TAT antibody, oligopeptide or oiganic molecule therapy may be especially desirable in elderly patients who do not tolerate the toxicity and side effects of chemotherapy well and in metastatic disease where radiation therapy has limited usefulness. The tumor targeting anti-TAT antibodies, oligopeptides and oiganic molecules of the invention are useful to alleviate TAT-expressing cancers upon initial diagnosis of the disease or during relapse. For therapeutic applications, the anti-TAT antibody, oligopeptide or oiganic molecule can be used alone, or in combination therapy with, e.g., hormones, antiangiogens, or radiolabelled compounds, or with surgery, cryotherapy, and/or radiotherapy. Anti-TAT antibody, oligopeptide or organic molecule treatment can be administered in conjunction with other forms of conventional therapy, either consecutively with, pre- or post-conventional therapy. Chemotherapeutic drugs such as TAXOTERE® (docetaxel), TAXOL® (palictaxel), estramustine and mitoxantrone are used in treating cancer, in particular, in good risk patients. In the present method of the invention for treating or alleviating cancer, the cancer patient can be administered anti-TAT antibody, oligopeptide or organic molecule in conjuction with treatment with the one or more of the preceding chemotherapeutic agents. In particular, combination therapy with palictaxel and modified derivatives (see, e.g., 95 EP0600517) is contemplated. The anti-TAT antibody, oligopeptide or organic molecule will be administered with a therapeutically effective dose of Ihe chemotherapeutic agent In another embodiment, the anti-TAT antibody, oligopeptide or organic molecule is administered in conjunction with chemotherapy to enhance the activity and efficacy of the chemotherapeutic agent, e.g., paclitaxel. The Physicians' Desk Reference (PDR) discloses dosages of these agents that have been used in treatment of various cancers. Hie dosing regimen and dosages of these aforementioned chemotherapeutic drugs that are therapeutically effective will depend on the particular cancer being treated, the extent of the disease and other factors familiar to the physician of skill in the art and can be "detennined by the physician. In one particular embodiment, a conjugate comprising an anti-TAT antibody, oligopeptide or organic molecule conjugated with a cytotoxic agent is administered to the patient Preferably, the immunoconjugate bound to the TAT protein is internalized by the cell, resulting in increased therapeutic efficacy of the immunoconjugate in killing the cancer cell to which it binds. In a preferred embodiment, the cytotoxic agent targets or interferes with the nucleic acid in the cancer cell. Examples of such cytotoxic agents are described above and include maytansinoids, calicheaznicins, ribonucleases and DNA endonucleases. The anti-TAT antibodies, oligopeptides, oiganic molecules or toxin conjugates thereof are administered to a human patient, in accord with known methods, such as intravenous administration, e.g.„ as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intracerobrospinal, subcutaneous, intra-articular, intrasynovial, intrathecal, oral, topical, or inhalation routes. Intravenous or subcutaneous administration of the antibody, oligopeptide or organic molecule is preferred. Other therapeutic regimens may be combined with the administration of the anti-TAT antibody, oligopeptide or organic molecule. The combined administration includes co-administration, using separate formulations or a single pharmaceutical formulation, and consecutive administration in either order, wherein preferably there is a time period while both (or all) active agents simultaneously exert their biological activities. Preferably such combined therapy results in a synergistic therapeutic effect. It may also be desirable to combine administration of the anti-TAT antibody or antibodies, oligopeptides or organic molecules, with administration of an antibody directed against another tumor antigen associated with the particular cancer. In another embodiment, the therapeutic treatment methods described involves the combined administration of an anti-TAT antibody (or antibodies), oligopeptides or organic molecules and one or more chemotherapeutic agents or growth inhibitory agents, including co-administration of cocktails of different chemotherapeutic agents. Chemotherapeutic agents include estramustine phosphate, prednimustine, cisplatin, 5-fluorouracil, melphalan, cyclophosphamide, hydroxyurea and hydroxyureataxanes (such as paclitaxel and doxetaxel) and/or anthracycline antibiotics. Preparation and dosing schedules for such chemotherapeutic agents may be used according to manufacturers' instructions or as determined empirically by Ihe skilled practitioner. Preparation and dosing schedules for such chemotherapy are also described in Chemotherapy Service Ed., M.C. Perry, Williams & Wilkins, Baltimore, MD (1992). Hie antibody, oligopeptide or organic molecule may be combined with an anti-hormonal compound; e.g., an anti-estrogen compound such as tamoxifen; an anti-progesterone such as onapristone (see, EP 616 812); or an 96 anti-androgen such as flutamids, in dosages known for such molecules. Where the cancer to be treated is androgen independent cancer, Ihe patient may previously have been subjected to anti-androgen therapy and, after the cancer becomes androgen independent, the anti-TAT antibody, oligopeptide or organic molecule (and optionally other agents as described herein) may be administered to the patient Sometimes, it may be beneficial to also co-administer a cardioprotectant (to prevent or reduce myocardial 5 dysfunction associated with the therapy) or one or more cytokines to the patient In addition to the above therapeutic regimes, the patient may be subjected to surgical removal of cancer cells and/or radiation therapy, before, simultaneously with, or post antibody, oligopeptide or oiganic molecule therapy. Suitable dosages for any of the above co-administered agents are those presently used and may be lowered due to the combined action (synergy) of the agent and anti-TAT antibody, oligopeptide or organic molecule. 10 For the prevention or treatment of disease, the dosage and mode of administration will be chosen by the physician according to known criteria. The appropriate dosage of antibody, oligopeptide or organic molecule will ^ depend on the type of disease to be treated, as defined above, the severity and course of the disease, whether the antibody, oligopeptide or organic molecule is administered for preventive or therapeutic purposes, previous therapy, the patient's clinical histoiy and response to the antibody, oligopeptide or oiganic molecule, and the 15 discretion of the attending physician. Ihe antibody, oligopeptide or oiganic molecule is suitably administered to the patient at one time or over a series of treatments. Preferably, the antibody, oligopeptide or oiganic molecule is administered by intravenous infusion or by subcutaneous injections. Depending on the type and severity of the disease, about 1 ng/kg to about 50 mg/kg body weight (e.g., about 0.1-15mg/kg/dose) of antibody can be an initial candidate dosage for administration to the patient whether, for example, by one or more separate 20 administrations, or by continuous infusion. A dosing regimen can comprise administering an initial loading dose of about 4 mg/kg, followed by a weekly maintenance dose of about 2 mg/kg ofthe anti-TAT antibody. However, other dosage regimens may be useful. A typical daily dosage might range from about 1 ng/kg to 100 mg/kg or more, depending on the factors mentioned above. For repeated administrations over several days or longer, depending on the condition, die treatment is sustained until a desired suppression of disease symptoms occurs. 25 Ihe progress of this therapy can be readily monitored by conventional methods and assays and based on criteria known to the physician or other persons of skill in the art Aside from administration of the antibody protein to the patient, the present application contemplates administration ofthe antibody by gene therapy. Such administration of nucleic acid encoding the antibody is encompassed by the expression "administering a therapeutically effective amount of an antibody". See, for 30 example, W096/07321 published March 14,1996 concerning the use of gene therapy to generate intracellular antibodies. There are two major approaches to getting the nucleic acid (optionally contained in a vector) into the patients cells; in vivo and ex vivo. For in vivo delivety the nucleic acid is injected directly into the patient, usually at the site where the antibody is required. For at vivo treatment, the patient's cells are removed, the nucleic acid 35 is introduced into these isolated cells and the modified cells are administered to the patient either directly or, for example, encapsulated within porous membranes which are implanted into the patient (see, e.g., U.S. Patent Nos. 4,892,538 and 5,283,187). There are a variety of techniques available for introducing nucleic acids into viable cells. 97 The techniques vary depending upon whether the nucleic acid is transferred into cultured cells in vitro, or in vivo in the cells of the intended host. Techniques suitable for the transfer of nucleic acid into mammalian cells in vitro include the use of liposomes, electroporation, microinjection, cell fusion, DEAE-dextran, the calcium phosphate precipitation method, etc. A commonly used vector for ex vivo delivery of the gene is a retroviral vector. The currently preferred in vivo nucleic acid transfer techniques include transfection with viral vectors 5 (such as adenovirus, Heipes simplex I virus, or adeno-associated virus) and lipid-based systems (useful lipids for lipid-mediated transfer of the gene are DOTMA, DOPE and DC-Choi, for example). For review of the currently known gene marking and gene therapy protocols see Anderson et aL, Science 256:808-813 (1992). See also WO 93/25673 and the references cited therein. The anti-TAT antibodies described can be in the different forms encompassed by the definition 10 of "antibody" herein. Thus, the antibodies include full length or intact antibody, antibody fragments, native sequence antibody or amino acid variants, humanized, chimeric or fusion antibodies, immunoconjugates, and functional fragments thereof. Li fusion antibodies an antibody sequence is fused to a heterologous polypeptide sequence. The antibodies can be modified in the Fc region to provide desired effector functions. As discussed in more detail in the sections herein, with the appropriate Fc regions, the naked antibody bound on the cell surface 15 can induce cytotoxicity, e.g., via antibody-dependent cellular cytotoxicity (ADCC) or by recruiting complement in complement dependent cytotoxicity, or some other mechanism. Alternatively, where it is desirable to eliminate or reduce effector function, so as to minimize side effects or therapeutic complications, certain other Fc regions may be used. In one embodiment, the antibody competes for binding or bind substantially to, the same epitope as the 20 antibodies of the invention. Antibodies having the biological characteristics of the present anti-TAT antibodies of the invention are also contemplated, specifically including the in vivo tumor targeting and any cell proliferation inhibition or cytotoxic characteristics. Methods of producing the above antibodies are described in detail herein. The present anti-TAT antibodies, oligopeptides and organic molecules are usefiil for treating a TAT-25 expressing cancer or alleviating one or more symptoms of the cancer in a mammal. Such a cancer includes prostate cancer, cancer of the urinary tract, lung cancer, breast cancer, colon cancer and ovarian cancer, more specifically, prostate adenocarcinoma, renal cell carcinomas, colorectal adenocarcinomas, lung adenocarcinomas, lung squamous cell carcinomas, and pleural mesothelioma. The cancers encompass metastatic cancers of any of the preceding. The antibody, oligopeptide or organic molecule is able to bind to at least a portion of the cancer cells 30 that express TAT polypqptide in the mammal. In a preferred embodiment, the antibody, oligopeptide or oiganic molecule is effective to destroy or kill TAT-expressing tumor cells or inhibit the growth of such tumor cells, in vitro or in vivo, upon binding to TAT polypeptide on the cell. Such an antibody includes a naked anti-TAT antibody (not conjugated to any agent). Naked antibodies that have cytotoxic or cell growth inhibition properties can be further harnessed with a cytotoxic agent to render them even more potent in tumor cell destruction. Cytotoxic 35 properties can be conferred to an anti-TAT antibody by, e.g., conjugating- the antibody with a cytotoxic agent, to form an immunoconjugate as described herein. The cytotoxic agent or a growth inhibitoiy agent is preferably a small molecule. Toxins such as calicheamicin or a maytansinoid and analogs or derivatives thereof, are preferable. 98 Also described is a composition comprising an anti-TAT antibody, oligopeptide or organic molecule ofthe invention, and a carrier. For the puiposes of treating cancer, compositions can be administered to the patient in need of such treatment, wherein the composition can comprise one or more anti-TAT antibodies present as an immunoconjugate or as the naked antibody. In a further embodiment, the compositions can comprise these antibodies, oligopeptides or organic molecules in combination with other therapeutic agents such as 5 cytotoxic or growth inhibitory agents, including chemotherapeutic agents. Also described are formulations comprising an anti-TAT antibody, oligopeptide or organic molecule of the invention, and a carrier, tn one embodiment, Ihe formulation is a therapeutic formulation comprising a pharmaceutically acceptable carrier. Also described is isolated nucleic acids encoding the anti-TAT antibodies. Nucleic acids encoding both the H and L chains and especially the hypervariable region residues, chains which encode 10 the native sequence antibody as well as variants, modifications and humanized versions of the antibody, are encompassed. Also described are methods useful for treating a TAT polypeptide-expressing cancer or " alleviating one or more symptoms of the cancer in a mammal, comprising administering a therapeutically effective amount of an anti-TAT antibody, oligopeptide or organic molecule to the mammal. The antibody, oligopeptide 15 or organic molecule therapeutic compositions can be administered short term (acute) or chronic, or intermittent as directed by physician. Also provided are methods of inhibiting the growth of, and killing a TAT polypeptide-expressing cell. Also described are kits and articles of manufacture comprising at least one anti-TAT antibody, oligopeptide or organic molecule. Kits containing anti-TAT antibodies, oligopeptides or organic molecules find 20 use, e.g., for TAT cell killing assays, for purification or immunoprecipitation of TAT polypeptide from cells. For example, for isolation and purification of TAT, the kit can contain an anti-TAT antibody, oligopeptide or oiganic molecule coupled to beads (e.g., sepharose beads). Kits can be provided which contain the antibodies, oligopeptides or oiganic molecules for detection and quantitation of TAT in vitro, e.g., in anELISA or a Western blot Such antibody, oligopeptide or organic molecule usefiil for detection may be provided with a label such as 25 a fluorescent or radiolabel. L. Articles of Manufacture and Kits Also described is an article of manufacture containing materials useful for the treatment of anti-TAT expressing cancer. The article of manufacture comprises a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, etc. « 30 The containers may be formed from a variety of materials such as glass or plastic. Ihe container holds a composition which is effective for treating the cancer condition and may have a sterile access port (for example the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). At least one active agent in the composition is an anti-TAT antibody, oligopeptide or oiganic molecule of the invention. The label or package insert indicates that the composition is used for treating cancer. The label 35 or package insert will further comprise instructions for administering the antibody, oligopeptide or organic molecule composition to the cancer patient Additionally, the article of manufacture may further comprise a second container comprising a pharmaceutically-acceptable buffer, such as bacteriostatic water for injection (BWFI), 99 phosphate-buffered saline, Ringer's solution and dextrose solution. It may further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes. Kits are also provided that are useful for various puiposes, e.g., for TAT-expressing cell killing assays, for purification or immunoprecipitation of TAT polypeptide from cells. For isolation and purification of TAT polypeptide, the kit can contain an anti-TAT antibody, oligopeptide or oiganic molecule coupled to beads (e.g., sepharose beads). Kits can be provided which contain the antibodies, oligopeptides or oiganic molecules for detection and quantitation of TAT polypeptide in vitro, e.g., in an BLISA or a Western blot As with the article of manufacture,' the kit comprises a container and a label or package insert on or associated with the container. The container holds a composition comprising at least one anti-TAT antibody, oligopeptide or organic molecule of the invention. Additional containers may be included that contain, e.g., diluents and buffers, control antibodies. The label or package insert may provide a description of the composition as well as instructions for the intended in vitro or diagnostic use. M. Uses for TAT Polypeptides and TAT-Polvoeptide Encoding Nucleic Acids Nucleotide sequences (or their complement) encoding TAT polypeptides have various applications in the art of molecular biology, including uses as hybridization probes, in chromosome and gene mapping and in the generation of anti-sense RNA and DNA probes. TAT-encoding nucleic acid will also be useful for the preparation of TAT polypeptides by the recombinant techniques described herein, wherein those TAT polypeptides may find use, for example, in the preparation of anti-TAT antibodies as described herein. The full-length native sequence TAT gene, or portions thereof may be used as hybridization probes for a cDNA library to isolate the foll-length TAT cDNA or to isolate still other cDNAs (for instance, those encoding naturally-occurring variants of TAT or TAT from other species) which have a desired sequence identity to the native TAT sequence disclosed herein. Optionally, the length of the probes will be about 20 to about 50 bases. The hybridization probes may be derived from at least partially novel regions of the full length native nucleotide sequence wherein those regions may be determined without undue experimentation or from genomic sequences including promoters, enhancer elements and introns of native sequence TAT. By way of example, a screening method will comprise isolating the coding legion of the TAT gene using the known DNA sequence to synthesize a selected probe of about 40 bases. Hybridization probes may be labeled by a variety of labels, including radionucleotides such as 32P or 35S, or enzymatic labels such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems. Labeled probes having a sequence complementary to that of the TAT gene of the present invention can be used to screen libraries of human cDNA, genomic DNA or mRNA to determine which members of such libraries the probe hybridizes to. Hybridization techniques are described in further detail in the Examples below. Any EST sequences disclosed in the present application may similarly be employed as probes, using the methods disclosed herein. Other useful fragments of the TAT-encoding nucleic acids include antisense or sense oligonucleotides comprising a singe-stranded nucleic acid sequence (either RNA or DNA) capable of binding to taiget TAT mRNA (sense) or TAT DNA (antisense) sequences. Antisense or sense oligonucleotides, according to tibe present invention, comprise a fragment of the coding region of TAT DNA. Such a fragment generally comprises at least about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense 100 oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, for example, Stein and Cohen (Cancer Res. 48:2659,1988) and van der Krol et al. (BinTechniqnes 6:958,1988). Binding of antisense or sense oligonucleotides to target nucleic acid sequences results in the formation of duplexes that block transcription or translation of the target sequence by one of several means, including enhanced degradation of the duplexes, premature termination of transcription or translation, or by other means. 5 Such methods are encompassed by Ihe present invention. The antisense oligonucleotides thus may be used to block expression of TAT proteins, wherein those TAT proteins may play a role in the induction of cancer in mammals. Antisense or sense Oligonucleotides further comprise oligonucleotides having modified sugar-phosphodiester backbones (or other sugar linkages, such as those described in WO 91/06629) and wherein such sugar linkages are resistant to endogenous nucleases. Such oligonucleotides with resistant sugar linkages are 10 stable in vivo (i.e., capable of resisting enzymatic degradation) but retain sequence specificity to be able to bind to taiget nucleotide sequences. Preferred intragenic sites for antisense binding include the region incorporating the translation initiation/start codon(5-AUG/ 5-ATG) ortermination/stop codon (5-UAA, 5-UAGand 5-UGA/5-TAA, 5-TAG and5,-TGA)oftheopenreadingftame(ORF).ofthegene. These regions refer to a portion of the mRNA or gene IS that encompasses from about 25 to about 50 contiguous nucleotides in either direction (Le., 5' or 3') from a translation initiation or termination codon. Other preferred regions for antisense binding include: introns; exons; intron-exon junctions; the open reading frame (ORF) or "coding region," which is the region between the translation initiation codon and the translation termination codon; the 5' cap of an mRNA which comprises an N7-methylated guanosine residue joined to the 5-most residue of the mRNA via a 5-5' triphosphate linkage and 20 includes 5' cap structure itself as well as the first 50 nucleotides adjacent to the cap; the 5' untranslated region (51TIR), the portion of an mRNA in the 5' direction from the translation initiation codon, and thus including nucleotides between the 5' cap site and the translation initiation codon of an mRNA or corresponding nucleotides on the gene; and the 31 untranslated region (3UTR), the portion of an mRNA in the 3' direction from the translation termination codon, and thus including nucleotides between the translation termination codon and 3' end of an 25 mRNA or corresponding nucleotides on the gene. Specific examples of preferred antisense compounds useful for inhibiting expression of TAT protons include oligonucleotides containing modified backbones or non-natural internucleoside linkages. Oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in Ihe backbone. For the purposes of this specification, and as sometimes referenced in 30 the art, modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides. Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotri-esters, methyl and other alkyl phosphonates including 3'-alkylene phosphonates, 5-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3-amino phosphoramidate 35 and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, selenophosphates and borano-phosphates having normal 3-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein one or more intemucleotide linkages is a 3' to 3', 5' 101 to 5' or 2' to 21 linkage. Preferred oligonucleotides having inverted polarity comprise a single 3* to 3' linkage at the 3-most internucleotide linkage i.e. a single inverted nucleoside residue which may be abasic (the nucleobase is missing or has a hydroxyl group in place thereof). Various salts, mixed salts and free acid forms are also included. Representative United States patents that teach the preparation of phosphorus-containing linkages include, but arenotlimitedto,U.S. PatNos.: 3,687,808; 4,469,863;4,476,301;5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5 5,278,302; 5,286,717; 5,321,131; 5,399,676;5,405,939; 5/153,496; 5,455,233;5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; 5,194,599; 5,565,555; 5,527,899; 5,721,218; 5,672,697 and ~ 5,625,050, each of which is herein incorporated by reference. Preferred modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl 10 or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thiofonnacetyl backbones; " methylene formacetyl and thiofonnacetyl backbones; riboacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; 15 amide backbones; and others having mixed N, O, S and CH.sub.2 component parts. Representative United States patents that teach the preparation of such oligonucleosides include, but are not limited to,. U.S. Pat Nos. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704: 5,623,070; 5,663,312; 5,633,360; 5,677,437; 5,792,608; 5,646,269 and5,677,439, each of which is herein incorporated 20 by reference. In other preferred antisense oligonucleotides, both the sugar and the internucleoside linkage, i.e., the backbone, of the nucleotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an oligonucleotide mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA 25 compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylgjycine backbone. Hie nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms ofthe amide portion of the backbone. Representative United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos.: 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al., Science, 30 1991,254,1497-1500. Preferred antisense oligonucleotides incorporate phosphorothioate backbones and/or heteroatom backbones, and inparticular-CHj-NH-O-CHj-, -CH2-N(CH3)-0-CH2- [known as amethylene(methylimino) orMMI backbone], -CH2-0-N(CH3)-CH2-, -CH^CHjJ-N^VCH,- and -O-NCCH^-^-CHj- [wherein the native phosphodiester backbone is represented as -0-P-0-CH2~] described in the above referenced U.S. Pat No. 5,489,677, 35 and the amide backbones of the above referenced U.S. Pat No. 5,602,240. Also preferred are antisense oligonucleotides having morpholino backbone structures of the above-referenced U.S. Pat No. 5,034,506. 102 Modified oligonucleotides may also contain one or more substituted sugar moieties. Preferred oligonucleotides comprise one of (be following at the 2' position: OH; F; O-alkyl, S-alkyl, orN-alkyl; O-alkenyl, S-alkeynyl, orN-alkenyl; O-alkynyl, S-allfynyl orN-alkynyl; orO-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C, to C10 alkyl or C2 to C10 alkenyl and alkynyl. Particularly preferred are O[((^)n0]mOT3,O(CH2)nOCH3J0(CH2)1^,O((^11(^,0(CH2)110Ml2)and0{CH2)n0N[(CH2)11CH3)]2,wheren and m are from 1 to about 10. Other preferred antisense oligonucleotides comprise one of the following at the 2' position: C, to C10 lower alkyl, substituted lower alkyl, alkenyl, alkynyl, alkaryl, aralkyl, O-alkaiyl or O-aralkyl, SH, SCHj, OCN, CI, Br, CN, CFj, OCF3, SOCH3> S02 CH3,0N02, N02,N3, NH^ heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. A preferred modification includes 2'-methoxyethoxy (2'-0-CH2CH20CH3, also known as 2'-0-(2-methoxyethyl) or 2-MOE) (Martin et al., Helv. Chim. Acta, 1995,78,486-504) Le., an alkoxyalkoxy group. A further preferred modification includes 2'-dimethylaminooxyethoxy, Le., a O(CH2)20N(CH3)2 group, also known as 2-DMAOE, as described in examples hereinbelow, and 2'-dimethylaminoethoxyethoxy (also known in the art as 2'-0-dimethylaminoethoxyethyl or 2'-DMAEOE), i.e„ 2*-0-C^-0-CJ^-N(Cej). • A further prefered modification includes Locked Nucleic Acids (LNAs) in which the 2-hydroxyl group is linked to the 3' or 4' carbon atom of the sugar ring thereby forming a bicyclic sugar moiely. The linkage is preferably a methely ne (-CHj-),, group bridging the 2' oxygen atom and the 4' caibon atom wherein n is 1 or 2. LNAs and preparation thereof are described in WO 98/39352 and WO 99/14226. Other preferred modifications include 2'-methoxy (2'-0-CH3), 2'-aminopropoxy (2'-OCH2CH2CH2 NHj), 2'-allyl (2'-CH2-CH=CH2), 2'-0-allyl (2'-0-CH2-CH=CE!) and 2-fluoro (2'-F). The 2'-modification may be in the arabino (up) position or ribo (down) position. A preferred 2'-arabino modification is 2'-F. Similar modifications may also be made at other positions on fixe oligonucleotide, particularly the 3* position of the sugar on the 3' terminal nucleotide or in 2-5' linked oligonucleotides and the 5' position of 5' terminal nucleotide. Oligonucleotides may also have sugar mimetics such as cyclobutyl moieties in place of the pentofiiranosyl sugar. Representative United States patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat Nos.: 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878;5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; 5,792,747; and5,700,920, each of which is herein incorporated by reference in its entirety. Oligonucleotides may also include nucleobase (often referred to in the art simply as "base") modifications or substitutions. As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5-halouracil and cytosine, 5-propynyl (-C=C-CH3 or -CH^-C^CH) uracil and cytosine and other alkynyl derivatives of pyrimidine bases, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl 103 and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7-methyladenine, 2-F-adenine, 2-amino-adenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3-deazaguanine and 3-deazaadenine. Further modified nucleobases include tricyclic pyrimidines such as phenoxazine cytidine(lH-pyrimido[5,4-b] [ l,4]benzoxazin-2(3H)-one), phenothiazine cytidine (lH-pyrimido[5,4-b][l,4]benzothia2in-2(3H)-one), G-clamps such as a substituted phenoxazine cytidine (e.g. 9-(2-aminoethoxy)-H-pyrimido[5,4-b][l,4]benzoxazin-2(3H)-one), carbazole cytidine (2H-pyrimido[4,5-b]mdol-2-one), pyridoindolecytidine (H-pyrido[3I,2l:4)5]pyrrolo[2,3-d]pyrimidin-2-one). Modified nucleobases may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2-aminopyridine and 2-pyridone. Further nucleobases include those disclosed in U.S. Pat No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858-859, Kroschwitz, J. I., ed. John Wiley & Sons, 1990, and those disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991,30,613. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the inventioa These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted purines, including 2-aminopropyladenine, 5-propynyluracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2.degree. C. (Sanghvi et al, Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are preferred base substitutions, even more particularly when combined with 2'-0-methoxyethyl sugar modifications. Representative United States patents that teach the preparation of modified nucleobases include, but are not limited to: U.S. Pat No. 3,687,808, as well as U.S. Pat Nos.: 4,845,205; 5,130,302; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121,5,596,091; 5,614,617; 5,645,985; 5,830,653; 5,763,588; 6,005,096; 5,681,941 and5,750,692, each of which is herein incorporated by reference. Another modification of antisense oligonucleotides chemically linking to the oligonucleotide one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. The described compounds can include conjugate groups covalently bound to functional groups such as primary or secondary hydroxyl groups. Conjugate groups of the invention include intercalated, reporter molecules, polyamines, polyamides, polyethylene glycols, polyethers, groups that enhance the pharmacodynamic properties ' of oligomers, and groups that enhance the pharmacokinetic properties of oligomers. Typical conjugates groups include cholesterols, lipids, cation lipids, phospholipids, cationic phospholipids, biotin, phenazine, folate, phenanthridine, anthraquinone, acridine, fluoresceins, ihodamines, coumarins, and dyes. Groups that enhance the pharmacodynamic properties, include groups that improve oligomer uptake, enhance oligomer resistance to degradation, and/or strengthen sequence-specific hybridization with RNA. Groups that enhance the pharmacokinetic properties, , include groups that improve oligomer uptake, distribution, metabolism or excretion. Conjugate moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989,86,6553-6556), cholic acid (Manoharan et al., Bioorg. Med. Chem. Let., 1994,4,1053-1060), a thioether, e.g., hexyl-S-tritylthiol (Manoharan et al., Ana N.Y. Acad. Sci., 1992,660,306-309; Manoharan et al., Bioorg. Med. Chem. Let, 1993,3,2765-2770), afhiocholesterol 104 (Oberhauser et al., Nucl. Acids Res., 1992,20,533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoarasetal.,EMBO J., 1991,10,1111-1118; Kabanovetal.,FEBS Lett, 1990,259,327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethyl-ammonium l,2-di-0-hexadecyl-rac-glycero-3-H-phosphonate (Manoharan etal., Tetrahedron Lett, 1995,36,3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Manoharan et al., 5 Nucleosides & Nucleotides, 1995,14,969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett, 1995, 36, 3651-3654), a palmityl moiety (Misbra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety. Oligonucleotides of the invention may also be conjugated to active drug substances, for example, aspirin, warfarin, phenylbutazone, ibuprofen, suprofen, fenbufen, ketoprofen, (SM+)-pranoprofen, carprofen, dansylsarcosine, 2,3,5-triiodobenzoic acid, flufenamic acid, 10 folinic acid, a benzotliiadiazide, chlorothiazide, a diazepine, indomethicin, a barbiturate, a cephalosporin, a sulfa drug, an antidiabetic, an antibacterial or an antibiotic. Oligonucleotide-drug conjugates and their preparation are described in U.S. patent application Ser. No. 09/334,130 (filed Jun. 15, 1999) and United States patents Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717,5,580,731; 5,580,731; 5,591,584 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046;4,587,044; 4,605,735; 4,667,025 15 4,762,779;4,789,737; 4,824,941;4,835,263;4,876,335;4,904,582;4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,29^,873; 5,317,098; 5,371,241,5,391,723 5,416,203,5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726: 5,597,696; 5,599,923; 5,599,928 and 5,688,941, each of which is herein incorporated by reference. It is not necessary for all positions in a given compound to be uniformly modified, and in feet more than 20 one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an oligonucleotide. Also described are antisense compounds which are chimeric compounds. "Chimeric" antisense compounds or "chimeras," in the context of this invention, are antisense compounds, particularly oligonucleotides, which contain two or more chemically distinct regions, each made up of at least one monomer unit, Le., a nucleotide in the case of an oligonucleotide compound. These oligonucleotides 25 typically contain at least one region wherein the oligonucleotide is modified so as to confer upon the oligonucleotide increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid. An additional region of the oligonucleotide may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNase H is a cellular endonuclease which cleaves the RNA strand of an RNA:DNA duplex. Activation of RNase H, therefore, results 30 in cleavage of the RNA target, thereby greatly enhancing Ihe efficiency of oligonucleotide inhibition of gene expression. Consequently, comparable results can often be obtained with shorter oligonucleotides when chimeric oligonucleotides are used, compared to phosphorothioate deoxyoligonucleotides hybridizing to the same target region. Chimeric antisense compounds of the invention may be formed as composite structures of two or more oligonucleotides, modified oligonucleotides, oligonucleosides and/or oligonucleotidemimetics as described above. 3 5 Preferred chimeric antisense oligonucleotides incorporate at least one 2' modified sugar (preferably 2'-0-(CHJ)r0-CHj) at the 3' terminal to confer nuclease resistance and a region with at least 4 contiguous 2'-H sugars to confer RNase H activity. Such compounds have also been referred to in the art as hybrids or gapmers. Preferred gapmers 105 have aregion of 2' modified sugars (preferably ^-O-fCH^-O-CHj) at the 3'-terminal and at the 5' terminal separated by at least one region having at least 4 contiguous 2'-H sugars and preferably incorporate phosphorothioate backbone linkages. Representative United States patents that teach the preparation of such hybrid structures include, but are not limited to, U.S. Pat Nos. 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711"; 5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922, each of which is herein incorporated by reference in its entirety. The antisense compounds described may be conveniently and routinely made through the well-known technique of solid phase synthesis. Equipment for such synthesis is sold by several vendors including, for example, Applied Biosystems (Foster Cily, Calif.). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is well known to use similar techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives. The compounds of the invention may also be admixed, encapsulated, conjugated or otherwise associated with other molecules, molecule structures or mixtures of compounds, as for example, liposomes, receptor targeted molecules, oral, rectal, topical or other formulations, for assisting in uptake, distribution and/or absorption. Representative United States patents that teach the preparation of such uptake, distribution and/or absorption assisting formulations include, but are not limited to, U.S.Pat Nos. 5,108,921; 5,354,844; 5,416,016; 5,459,127; 5,521,291; 5,543,158; 5,547,932; 5,583,020; 5,591,721;4,426,330;4,534,899; 5,013,556; 5,108,921; 5,213,804; 5,227,170; 5,264,221; 5,356,633; 5,395,619; 5,416,016; 5,417,978; 5,462,854; 5,469,854; 5,512,295; 5,527,528; 5,534,259; 5,543,152; 5,556,948; 5,580,575; and5,595,756, each of which is herein incorporated by reference. Other examples of sense or antisense oligonucleotides include those oligonucleotides which are covalently linked to organic moieties, such as those described in WO 90/10048, and other moieties that increases affinity of the oligonucleotide for a target nucleic acid sequence, such as poly-(L-lysine). Further still, intercalating agents, such as ellipticine, and alkylating agents or metal complexes may be attached to sense or antisense oligonucleotides to modify binding specificities of the antisense or sense oligonucleotide for the target nucleotide sequence. Antisense or sense oligonucleotides may be introduced into a cell containing the target nucleic acid sequence by any gene transfer method, including, for example, CaP04-mediated DNA transfection, electroporation, or by using gene transfer vectors such as Epstein-Barr virus. In a preferred procedure, an antisense or sense oligonucleotide is inserted into a suitable retroviral vector. A cell containing the target nucleic acid sequence is contacted with the recombinant retroviral vector, either in vivo or ex vivo. Suitable retroviral vectors include, but are not limited to, those derived from the murine retrovirus M-MuLV, N2 (a retrovirus derived from M-MuLV), or the double copy vectors designated DCT5 A, DCT5B and DCT5C (see WO 90/13641). Sense or antisense oligonucleotides also may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surfece receptors, growth factors, other cytokines, or other ligands that bind to cell surfece receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with Ihe ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. 106 Alternatively, a sense or an antisense oligonucleotide may be introduced into a cell containing the taiget nucleic acid sequence by formation of an oligonucleotide-lipid complex, as described in WO 90/10448. The sense or antisense oligonucleotide-lipid complex is preferably dissociated within the cell by an endogenous lipase. Antisense or sense RNA or DNA molecules are generally at least about 5 nucleotides in length, alternatively atleast about 6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,35,40, 45,50,55,60,65,70,75,80,85,90,95,100,105,110,115,120,125,130,135,140,145,150,155,160,165,170,175,180, 185,190,195,200,210,220,230,240,250,260,270,280,290,300,310,320,330,340,350,360,370,380,390,400,410, 420,430,440,450,460,470,480,490,500,510,520,530,540,550,560,570,580,590,600,610,620,630,640,650,660, 670,680,690,700,710,720,730,740,750,760,770,780,790,800,810,820,830,840,850,860,870,880,890,900,910, 920,930,940,950,960,970,980,990, or 1000 nucleotides in length, wherein in this context Ihe term "about" means the referenced nucleotide sequence length plus or minus 10% of that referenced length. The probes may also be employed in PCR techniques to generate a pool of sequences for identification of closely related TAT coding sequences. Nucleotide sequences encoding a TAT can also be used to construct hybridization probes for mapping the gene which encodes that TAT and for the genetic analysis of individuals with genetic disorders. The nucleotide sequences provided herein may be mapped to a chromosome and specific regions of a chromosome using known techniques, such as in situ hybridization, linkage analysis against known chromosomal markers, and hybridization screening with libraries. • When the coding sequences for TAT encode a protein which binds to another protein (example, where the TAT is a receptor), the TAT can be used in assays to identify the other proteins or molecules involved in the binding interaction. By such methods, inhibitors of the receptor/ligand binding interaction can be identified. Proteins involved in such binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction. Also, the receptor TAT can be used to isolate correlative ligand(s). Screening assays can be designed to find lead compounds that mimic the biological activity of a native TAT or a receptor for TAT. Such screening assays will include assays amenable to high-throughput screening of chemical libraries, making them particularly suitable for identifying small molecule drug candidates. Small molecules contemplated include synthetic organic or inorganic compounds. The assays can be performed in a variety of formats, including protein-protein binding assays, biochemical screening assays, immunoassays and cell based assays, which are well characterized in the art. Nucleic acids which encode TAT or its modified foims can also be used to generate either transgenic animals or "knock out" animals which, in turn, are useful in the development and screening of therapeutically useful reagents. A transgenic animal (e.g., a mouse or rat) is an animal having cells that contain a transgene, which transgene was introduced into the animal or an ancestor of the animal at a prenatal, e.g., an embryonic stage. A transgene is a DNA which is integrated into the genome of a cell from which a transgenic animal develops. In one embodiment, cDNA encoding TAT can be used to clone genomic DNA encoding TAT in accordance with established techniques and the genomic sequences used to generate transgenic animals that contain cells which express DNA encoding TAT. Methods for generating transgenic animals, particularly animals such as mice or rats, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866 and 4,870,009. 107 Typically, particular cells would be targeted for TAT transgene incorporation with tissue-specific enhancers. Transgenic animals that include a copy of a transgene encoding TAT introduced into die gam line of the animal at an embryonic stage can be used to examine the effect of increased expression of DNA encoding TAT. Such animals can be used as tester animals for reagents thought to confer protection from, for example, pathological conditions associated with its overexpressioa In accordance with this facet of the invention, an animal is treated with the reagent and a reduced incidence of the pathological condition, compared to untreated animals bearing die transgene, would indicate a potential tiierapeutic intervention for the pathological condition Alternatively, non-human homoiogues of TAT can be used to constructs TAT "knock out" animal which has a defective or altered gene encoding TAT as a result of homologous recombination between the endogenous gene encoding TAT and altered genomic DNA encoding TAT introduced into an embryonic stem cell of the animal. For example, cDNA encoding TAT can be used to clone genomic DNA encoding TAT in accordance with established techniques. A portion of the genomic DNA encoding TAT can be deleted or replaced with another gene, such as a gene encoding a selectable marker which can be used to monitor integratioa Typically, several kilobases of unaltered flanking DNA (both at die 5' and 3' ends) are included in the vector [see e.g., Thomas and Capecchi, Cell. 51:503 (1987) for a description of homologous recombination vectors]. The vector is introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced DNA has homologously recombined with the endogenous DNA are selected [see e.g., Li et al., Cell. 69:915 (1992)]. The selected cells are then injected into a blastocyst of an animal (e.g., a mouse or rat) to form aggregation chimeras [see e.g., Bradley, in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp. 113-152]. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to torn to create a "knock out" animal. Progeny harboring the homologously recombined DNA in their germ cells can be identified by standard techniques and used to breed animals in which all cells of die animal contain the homologously recombined DNA. Knockout animals can be characterized for instance, for their ability to defend against certain pathological conditions and for their development of pathological conditions due to absence of the TAT polypeptide. Nucleic acid encoding die TAT polypeptides may also be used in gene therapy. In gene therapy applications, genes are introduced into cells in order to achieve in vivo synthesis of a therapeutically effective genetic product, for example for replacement of a defective gene. "Gene therapy" includes both conventional gene therapy where a lasting effect is achieved by a single treatment, and the administration of gene therapeutic agents, which involves die one time or repeated administration of a therapeutically effective DNA or mRNA. Antisense RNAs and DNAs can be used as therapeutic agents for blocking die expression of certain genes in vivo. It has already been shown that short antisense oligonucleotides can be imported into cells where they act as inhibitors, despite their low intracellular concentrations caused by their restricted uptake by the cell membrane. (Zamecnik et al., Proc. Nad. Acad. Sci. USA 83:4143-4146 [1986]). The oligonucleotides can be modified to enhance then-uptake, e.g. by substituting their negatively charged phosphodiester groups by uncharged groups. There are a variety of techniques available for introducing nucleic acids into viable cells. The techniques vary depending upon whether the nucleic acid is transferred into cultured cells in vitro, or in vivo in the cells of the intended host Techniques suitable for die transfer of nucleic acid into mammalian cells in vitro include the 108 use of liposomes, electroporation, microinjection, cell fusion, DEAE-dextran, the calcium phosphate precipitation method, etc. The currently preferred in vivo gene transfer techniques include transfection with viral (typically retroviral) vectors and viral coat protein-liposome mediated transfection (Dzau et al., Trends in Biotechnology 11, 205-210 [1993]). In some situations it is desirable to provide the nucleic acid source with an agent that targets the target cells, such as an antibody specific for a cell surface membrane protein or the target cell, a ligand for a receptor on Ihe taiget cell, etc. Where liposomes are employed, proteins which bind to a cell surface membrane protein associated with endocytosis may be used for targeting and/or to facilitate uptake, e.g. capsid proteins or fragments thereof tropic for a particular cell type, antibodies for proteins which undergo internalization in cycling; proteins that target intracellular localization and enhance intracellular half-life. The technique of receptor-mediated endocytosis is described, for example, by Wu et al., J.Biol. Chem. 262,4429-4432 (1987); and Wagner et al., Proc. Natl. Acad. Sci. USA 87,3410-3414 (1990). For review of gene marking and gene therapy protocols see Anderson et al., Science 256, 808-813 (1992). The nucleic acid molecules encoding the TAT polypeptides or fragments thereof described herein are useful for chromosome identification. In this regard, there exists an ongoing need to identify new chromosome markers, since relatively few chromosome marking reagents, based upon actual sequence data are presently available. Each TAT nucleic acid molecule of the present invention can be used as a chromosome marker. The TAT polypeptides and nucleic acid molecules described may also be used diagnostically for tissue typing, wherein the TAT polypeptides of the present invention may be differentially expressed in one tissue as compared to another, preferably in a diseased tissue as compared to a normal tissue of the same tissue type. TAT nucleic acid molecules will find use for generating probes for PCR, Northern analysis, Southern analysis and Western analysis. Described are methods of screening compounds to identify those that mimic the TAT polypeptide (agonists) or prevent the effect of the TAT polypeptide (antagonists). Screening assays for antagonist drug candidates are designed to identify compounds that bind or complex with the TAT polypeptides encoded by the genes identified herein, or otherwise interfere with the interaction of the encoded polypeptides with other cellular proteins, including e.g., inhibiting the expression of TAT polypeptide from cells. Such screening assays will include assays amenable to high-throughput screening of chemical libraries, making them particularly suitable for identifying small molecule drug candidates. The assays can be performed in a variety of formats, including protein-protein binding assays, biochemical screening assays, immunoassays, and cell-based assays, which are well characterized in the art. All assays for antagonists are common in that they call for contacting the drug candidate with a TAT polypeptide encoded by a nucleic acid identified herein under conditions and for a time sufficient to allow these two components to interact. In binding assays, Ihe interaction is binding and the complex formed can be isolated or detected in the reaction mixture. In a particular embodiment, the TAT polypeptide encoded by the gene identified herein or the drug candidate is immobilized on a solid phase, e.g., on a microtiter plate, by covalent or non-covalent attachments. Non-covalent attachment generally is accomplished by coating the solid surfece with a solution of the TAT polypeptide and drying. Alternatively, an immobilized antibody, e.g., a monoclonal antibody, specific for the TAT 109 polypeptide to be immobilized can be used to anchor it to a solid surfece. The assay is performed by adding the non-immobilized component, which may be labeled by a detectable label, to the immobilized component, e.g., the coated surfece containing the anchored component When the reaction is complete, the non-reacted components are removed, e.g., by washing, and complexes anchored on the solid surface are detected. When the originally non-immobilized component carries a detectable label, the detection of label immobilized on the surface indicates that complexing occurred. Where the originally non-immobilized component does not carry a label, complexing can be detected, for example, by using a labeled antibody specifically binding the immobilized complex. If the candidate compound interacts with but does not bind to a particular TAT polypqptide encoded by a gene identified herein, its interaction with that polypeptide can be assayed by methods well known for detecting protein-protein interactions. Such assays include traditional approaches, such as, e.g., cross-linking, co-immunoprecipitation, and co-purification through gradients or chromatographic columns. In addition, protein-protein interactions can be monitored by using a yeast-based genetic system described by Fields and co-workers (Fields and Song-Nature ^London).340:245-246 (1989); Chien et al.. Proc. Natl. Acad. Sci. USA. 88:9578-9582(1991)) as disclosed by Chevray and Nathans, Proc. Natl. Acad. Sci. USA. 89: 5789-5793 (1991). Many transcriptional activators, such as yeast OAL4, consist of two physically discrete modular domains, one acting as the DNA-binding domain, the other one functioning as the transcription-activation domain. The yeast expression system described in the foregoing publications (generally referred to as the "two-hybrid system") takes advantage of this property, and employs two hybrid proteins, one in which the taiget protein is fused to the DNA-binding domain of GAL4, and another, in which candidate activating proteins are fused to the activation domain. The expression of a GALl-focZ reporter gene under control of a GAL4-activated promoter depends on reconstitution of GAL4 activity via protein-protein interaction. Colonies containing interacting polypeptides are detected with a chromogenic substrate for P-galactosidase. A complete kit (MATCHMAKER™) for identifying protein-protein interactions between two specific proteins using the two-hybrid technique is commercially available from Clontech. This system can also be extended to map protein domains involved in specific protein interactions as well as to pinpoint amino acid residues that are crucial for these interactions. Compounds that interfere with the interaction of a gene encoding a TAT polypeptide identified herein and other intra- or extracellular components can be tested as follows: usually a reaction mixture is prepared containing the product of the gene and the intra- or extracellular component under conditions and for a time allowing for the interaction and binding of the two products. To test the ability of a candidate compound to inhibit binding, the reaction is run in the absence and in the presence of the test compound. In addition, a placebo may be added to a third reaction mixture, to serve as positive control. The binding (complex formation) between the test compound and the intra- or extracellular component present in the mixture is monitored as described hereinabove. The formation of a complex in the control reactions) but not in the reaction mixture containing the test compound indicates that the test compound interferes with the interaction of the test compound and its reaction partner. To assay for antagonists, the TAT polypeptide may be added to a cell along with the compound to be screened for a particular activity and the ability of the compound to inhibit die activity of interest in the presence of the TAT polypeptide indicates that the compound is an antagonist to the TAT polypeptide. Alternatively, 110 antagonists may be detected by combining the TAT polypeptide and a potential antagonist with membrane-bound TAT polypeptide receptors or recombinant receptors under appropriate conditions for a competitive inhibition assay. The TAT polypqptide can be labeled, such as by radioactivity, such that the number of TAT polypqptide molecules bound to the receptor can be used to determine the effectiveness of the potential antagonist. The gene encoding the receptor can be identified by numerous methods known to those of skill in the art, for example, ligand 5 panning and FACS sorting. Coligan et al., Current Protocols in hnmun.. 1(2): Chapter 5 (1991). Preferably, expression cloning is employed wherein polyadenylated RNA is prepared from a cell responsive to the TAT polypeptide and a cDNA library created from this RNA is divided into pools and used to transfect COS cells or other cells that are not responsive to the TAT polypeptide. Transfected cells that are grown on glass slides are exposed to labeled TAT polypeptide. The TAT polypeptide can be labeled by a variety of means including 10 iodination or inclusion of a recognition site for a site-specific protein kinase. Following fixation and incubation, the slides are subjected to autoradiographic analysis. Positive pools are identified and sub-pools are prepared and re-transfected using an interactive sub-pooling and re-screening process, eventually yielding a single clone that " encodes the putative receptor. As an alternative approach for receptor identification, labeled TAT polypeptide can be photoaffinity-15 linked with cell membrane or extract preparations that express the receptor molecule. Cross-linked material is resolved by PAGE and exposed to X-ray film. The labeled complex containing the receptor can be excised, resolved into peptide fiagments, and subjected to protein micro-sequencing. The amino acid sequence obtained from micro- sequencing would be used to design a set of degenerate oligonucleotide probes to screen a cDNA library to identify the gene encoding the putative receptor. 20 In another assay for antagonists, mammalian cells or a membrane preparation expressing the receptor would be incubated with labeled TAT polypeptide in the presence of the candidate compound. The ability of the compound to enhance or block this interaction could then be measured. More specific examples of potential antagonists include an oligonucleotide that binds to die fusions of immunoglobulin with TAT polypeptide, and, in particular, antibodies including, without limitation, poly- and 25 monoclonal antibodies and antibody fragments, single-chain antibodies, anti-idiotypic antibodies, and chimeric or humanized versions of such antibodies or fragments, as well as human antibodies and antibody fragments. Alternatively, a potential antagonist may be' a closely related protein, for example, a mutated form of the TAT polypeptide that recognizes the receptor but imparts no effect, thereby competitively inhibiting the action of the TAT polypeptide. 30 Another potential TAT polypeptide antagonist is an antisense RNA or DNA construct prepared using antisense technology, where, e.g., an antisense RNA or DNA molecule acts to block directly the translation of mRNA by hybridizing to targeted mRNA and preventing protein translation. Antisense technology can be used to control gene expression through triple-helix formation or antisense DNA or RNA, both of which methods are based on binding of a polynucleotide to DNA or RNA. For example, the 5' coding portion of the polynucleotide 35 sequence, which encodes the mature TAT polypeptides herein, is used to design an antisense RNA oligonucleotide of from about 10 to 40 base pairs in length. A DNA oligonucleotide is designed to be complementary to a region of the gene involved in transcription (triple helix - see Lee et al., Nucl. Acids Res.. 6:3073 111 (1979); Cooney et al., Science. 241: 456 (1988); Dervan et al., Science. 251:1360 (1991)), thereby preventing transcription and the production of the TAT polypeptide. The antisense RNA oligonucleotide hybridizes to the mRNA in vivo and blocks translation of the mRNA molecule into the TAT polypeptide (antisense - Okano, Neurochem.. 56:560 (1991); Oligodeoxvnudeotides as Antisenap- Inhibitors of Gene Expression (CR.C Press: Boca Raton, FL, 1988). The oligonucleotides described above can also be delivered to cells such that the antisense RNA 5 or DNA may be expressed in vivo to inhibit production of the TAT polypeptide. When antisense DNA is used, oligodeoxyribonucleotides derived from the translation-initiation site, e.g., between about -10 and +10 positions of the target gene nucleotide sequence, are preferred. ... Potential antagonists include small molecules that bind to Ihe active site, the receptor binding site, or growth factor or other relevant binding site of the TAT polypeptide, thereby blocking (he normal biological activity 10 of die TAT polypeptide. Examples of small molecules include, but are not limited to, small peptides orpeptide-like molecules, preferably soluble peptides, and synthetic non-peptidyl oiganic or inorganic compounds. Ribozymes are enzymatic RNA molecules capable of catalyzing the specific cleavage ofRNA. Ribozymes act by sequence-specific hybridization to the complementary taiget RNA, followed by endonucleolytic cleavage. Specific ribozyme cleavage sites within a potential RNA target can be identified by known techniques. For further 15 details see, e.g., Rossi, Current Biology. 4:469-471 (1994), and PCT publication No. WO 97/33551 (published September 18,1997). Nucleic acid molecules in triple-helix formation used to inhibit transcription should be single-stranded and composed of deoxynucleotides. The base composition of these oligonucleotides is designed such that it promotes triple-helix formation via Hoogsteen base-pairing rules, which generally require sizeable stretches of 20 purines or pyrimidines on one strand of a duplex. For further details see, e.g., PCT publication No. WO 97/33551, supra. These small molecules can be identified by any one or more of the screening assays discussed hereinabove and/or by any other screening techniques well known for those skilled in die art Isolated TAT polypeptide-encoding nucleic acid can be used herein for recombinandy producing TAT 25 polypeptide using techniques well known in the art and as described herein. In turn, the produced TAT polypeptides can be employed for generating anti-TAT antibodies using techniques well known in die art and as described herein. Antibodies specifically binding a TAT polypeptide identified herein, as well as other molecules identified by die screening assays disclosed hereinbefore, can be administered for the treatment of various disorders, 30 including cancer, in die form of pharmaceutical compositions. If the TAT polypeptide is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, lipofections or liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitoiy fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-35 region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al.. Proc. Nafl. Acad. Sci. USA. 90:7889-7893 (1993). 112 The formulation herein may also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition may comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent Such molecules are suitably present in combination in amounts that are effective for the purpose intended. The following examples ate offered for illustrative puiposes only, and are not intended to limit the scope of the present invention in any way. All patent and literature references cited in the present specification are hereby incorporated by reference in their entirety. 10 15 20 25 30 35 40 EXAMPLES Commercially available reagents referred to in the examples were used according to manufacturer's instructions unless otherwise indicated. The source of those cells identified in the following examples, and throughout the specification, by ATCC accession numbers is the American Type Culture Collection, Manassas, VA. KXTAMPT JR. 1: Tissue Expression Profiling Using GeneExpress® A proprietary database containing gene expression information (GeneExpress®, Gene Logic Inc., Gaithersburg, MD) was analyzed in an attempt to identify polypeptides (and their encoding nucleic acids) whose expression is significantly upregulated in a particular tumor tissue(s) of interest as compared to other tumor(s) and/or normal tissues. Specifically, analysis of the GeneExpress® database was conducted using either software available through Gene Logic Inc., Gaithersburg, MD, for use with Ihe GeneExpress® database or with proprietary software written and developed at Genentech, Inc. for use with the GeneExpress® database. The rating of positive hits in the analysis is based upon several criteria including, for example, tissue specificity, tumor specificity and expression level in normal essential and/or normal proliferating tissues. The following is a list of molecules whose tissue expression profile as determined from an analysis of the GeneExpress® database evidences high tissue expression and significant upiegulation of expression in a specific tumor or tumors as compared to other tumor(s) and/or normal tissues and optionally relatively low expression in normal essential and/or normal proliferating tissues. As such, the molecules listed below are excellent polypeptide targets for the diagnosis and therapy of cancer in mammals. Molecule DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) DNA64888-1542 (TAT393) upregulation of expression in: bone tumor breast tumor cervical tumor colon tumor rectum tumor endometrial tumor kidney tumor liver tumor lung tumor as compared to: normal bone tissue normal breast tissue normal cervical tissue normal colon tissue normal rectum tissue normal endometrial tissue normal esophageal tissue normal kidney tissue normal liver tissue normal lung tissue 113 Molecule upreeulation of expression in: as compared to: DNA64888-1542 (TAT393) ovarian tumor normal ovarian tissue DNA64888-1542 (TAT393) pancreatic tumor normal pancreatic tissue DNA64888-1542 (TAT393) skin tumor normal skin tissue DNA64889-1541 (TAT394) bone tumor normal bone tissue DNA64889-1541 (TAT394) breast tumor normal breast tissue DNA64889-1541 (TAT394) cervical tumor normal cervical tissue DNA64889-1541 (TAT394) colon tumor normal colon tissue DNA64889-1541 (TAT394) rectum tumor normal rectum tissue DNA64889-1541 (TAT394) endometrial tumor normal endometrial tissue DNA64889-1541 (TAT394) esophageal tumor normal esophageal tissue DNA64889-1541 (TAT394) kidney tumor normal kidney tissue DNA64889-1541 (TAT394) liver tumor normal liver tissue DNA64889-1541 (TAT394) lung tumor normal lung tissue DNA64889-1541 (TAT394) ovarian tumor normal ovarian tissue DNA64889-1541 (TAT394) pancreatic tumor normal pancreatic tissue DNA64889-1541 (TAT394) skin tumor normal skin tissue DNA57700-1408 (TAT395) bone tumor normal bone tissue DNA57700-1408 (TAT395) breast tumor normal breast tissue DNA57700-1408 (TAT395) cervical tumor normal cervical tissue DNA57700-1408 (TAT395) colon tumor normal colon tissue DNA57700-1408 (TAT395) rectum tumor normal rectum tissue DNA57700-1408 (TAT395) endometrial tumor normal endometrial tissue DNA57700-1408 CTAT395) esophageal tumor normal esophageal tissue DNA57700-1408 (TAT395) kidney tumor normal kidney tissue DNA57700-1408 (TAT395) liver tumor normal liver tissue DNA57700-1408 (TAT395) lung tumor normal lung tissue DNA57700-1408 (TAT395) ovarian tumor normal ovarian tissue DNA57700-1408 (TAT395) pancreatic tumor normal pancreatic tissue DNA57700-1408 (TAT395) skin tumor normal skin tissue F.T AMPT .K Microarrav Analysis to Detect Ubregulation of TAT Polypeptides in Cancerous Tumors Nucleic acid microarrays, often containing thousands of gene sequences, are useful for identifying differentially expressed genes in diseased tissues as compared to their normal counterparts. Using nucleic acid microarrays, test and control mRNA samples from test and control tissue samples are reverse transcribed and labeled to generate cDNA probes. The cDNA probes are then hybridized to an array of nucleic acids immobilized on a solid support The array is configured such that the sequence and position of each member of the array is known. For example, a selection of genes known to be expressed in certain disease states may be arrayed on a solid support Hybridization of a labeled probe with a particular array member indicates that the sample from which Ihe probe was derived expresses that gene. If the hybridization signal of a probe from a test (disease tissue) sample is greater than hybridization signal of a probe from a control (normal tissue) sample, the gene or genes overexpressed in the disease tissue are identified. The implication of this result is that an overexpressed protein in a diseased tissue is useful not only as a diagnostic marker for the presence of the disease condition, but also as a therapeutic target for treatment of the disease condition. The methodology of hybridization of nucleic acids and microarray technology is well known in the art In one example, the specific preparation of nucleic acids for hybridization and probes, slides, and hybridization conditions are all detailedihPCTPatent Application Serial No. PCT/US01/10482, filed onMarch30,2001 and which is herein incorporated by reference. 114 In the present example, psoriatic skin and normal skin samples were studied using microarray analysis in an attempt to identify those polypeptides which are overexpressed or underexpressed in psoriatic skin relative to normal skin. The results from these analyses demonstrated that the expression of TAT393 polypeptides is significantly and reproduciblydown regulated in psoriatic skin samples as compared to normal skin samples. As such, TAT393 polypeptides appear to play a protective role against the development of psoriasis. Therefore, these data demonstrate that TAT393 polypeptides will find use for both the prevention and therapeutic treatment of psoriatic conditions. Moreover, metibiods of diagnosing the presence of a psoriatic condition in a mammal comprising determining the expression level of a TAT393 polypeptide in a test skin tissue sample and a normal skin tissue sample, wherein a lower expression level in the test sample as compared to the normal sample is indicative of the presence of a psoriatic condition in the test sample. The results from these analyses also demonstrated that the expression of TAT394 polypeptides is significantly and reproducibly upregulated in psoriatic skin samples as compared to normal skin samples. As such, TAT394 polypeptides appear to play a causative role in the development of psoriasis. Therefore, these data demonstrate that antagonists of TAT394 polypeptides will find use for both the prevention and therapeutic treatment of psoriatic conditions. Moreover, methods of diagnosing the presence of a psoriatic condition in a mammal comprising detennining die expression level of a TAT394 polypeptide in a test skin tissue sample and a normal skin tissue sample, wherein a higher expression level in the test sample as compared to the normal sample is indicative of the presence of a psoriatic condition in the test sample. EXAMPLE 3: Use of TAT as a hybridization nrobe The following method describes use of a nucleotide sequence encoding TAT as a hybridization probe for, i.e., diagnosis of the presence of a tumor in a mammal. DNA comprising the coding sequence of foil-length or mature TAT as disclosed herein can also be . employed as a probe to screen for homologous DNAs (such as those encoding naturally-occurring variants of TAT) in human tissue cDNA libraries or human tissue genomic libraries. Hybridization and washing of filters containing either library DNAs is performed under the following high stringency conditions. Hybridization of radiolabeled TAT-derived probe to the filters is performed in a solution of 50% formamide, 5x SSC, 0.1% SDS, 0.1% sodium pyrophosphate, 50 mM sodium phosphate, pH 6.8, 2x Denhardfs solution, and 10% dextran sulfate at 42°C for 20 hours. Washing of the filters is performed in an aqueous solution of O.lx SSC and 0.1% SDS at 42°C. DNAs having a desired sequence identity with the DNA encoding full-length native sequence TAT can then be identified using standard techniques known in the art EXAMPLE 4: Expression of TAT in £. coli This example illustrates preparation of an unglycosylated form of TAT by recombinant expression in E. coll The DNA sequence encoding TAT is initially amplified using selected PCR primers. The primers should contain restriction enzyme sites which correspond to Ihe restriction enzyme sites on the selected expression 115 vector. A variety of expression vectors may be employed. An example of a suitable vector is pBR322 (derived from E. colt; see Bolivar et al., Gene. 2:95 (1977)) which contains genes forampicillin and tetracycline resistance. The vector is digested with restriction enzyme and dephosphorylated. The PCR. amplified sequences are then ligated into die vector. The vector will preferably include sequences which encode for an antibiotic resistance gene, a tip promoter, a polyhis leader (including the first six STH codons, polyhis sequence, and enterokinase cleavage site), the TAT coding region, lambda transcriptional terminator, and an argU gene. The ligation mixture is then used to transform a selected E. coli strain using the methods described in Sambrook et al., supra. Transformants are identified by their ability to grow on LB plates and antibiotic resistant colonies are then selected. Plasmid DNA can be isolated and confirmed by restriction analysis and DNA sequencing. Selected clones can be grown overnight in liquid culture medium such as LB broth supplemented with antibiotics. The overnight culture may subsequently be used to inoculate a larger scale culture. The cells are then grown to a desired optical density, during which the expression promoter is turned on. After culturing the cells for several more hours, the cells can be harvested by centrifugation. The cell pellet obtained by the centrifugation can be solubilized using various agents known in the art, and the solubilized TAT protein can then be purified using a metal chelating column under conditions that allow tight binding of the protein. TAT may be expressed in E. coli in a poly-His tagged form, using the following procedure. The DNA encoding TAT is initially amplified using selected PCR primers. The primers will contain restriction enzyme sites which correspond to the restriction enzyme sites on the selected expression vector, and other useful sequences providing for efficient and reliable translation initiation, rapid purification on a metal chelation column, and proteolytic removal with enterokinase. The PCR-amplified, poly-His tagged sequences are then ligated into an expression vector, which is used to transform an E. coli host based on strain 52 (W3110 fuhA(tonA) Ion galE rpoHts(htpRts) clpP(lacIq). Transformants are first grown in LB containing 50 mg/ml caibenicillin at 30°C with shaking until an O.D.6OO of 3-5 is reached. Cultures are then diluted 50-100 fold into CRAP media (prepared by mixing 3.57 g(NH4)2SO„,0.71 g sodium citrate»2H20,1.07 gKCl, 5.36 g Difco yeast extract, 5.36 g ShefiBeldhycase SF in 500 mL water, as well as 110 mM MPOS, pH 7.3,0.55% (w/v) glucose and 7 mM MgS04) and grown for approximately20-30hours at300C with shaking. Samples are removed to verify expression by SDS-PAGE analysis, and the bulk culture is centrifiiged to pellet the cells. Cell pellets are frozen until purification and refolding. E. coli paste from 0.5 to 1 L fermentations (6-10 g pellets) is resuspended in 10 volumes (w/v) in 7 M guanidine, 20 mM Tris, pH 8 buffer. Solid sodium sulfite and sodium tetrathionate is added to make final concentrations of 0.1M and 0.02 M, respectively, and the solution is stirred overnight at 4°C. This step results in a denatured protein with all cysteine residues blocked by sulfitolization. The solution is centrifiiged at 40,000 ipm in a Beckman Ultracentifuge for 30 min. The supernatant is diluted with 3-5 volumes of metal chelate column buffer (6 M guanidine, 20 mM Tris, pH 7.4) and filtered through 0.22 micron filters to clarify. The clarified extract is loaded onto a 5 ml Qiagen Ni-NTA metal chelate column equilibrated in the metal chelate column buffer. The column is washed with additional buffer containing 50 mM imidazole (Calbiochem, Utrol grade), pH 7.4. The protein is eluted with buffer containing 250 mM imidazole. Fractions containing the desired protein are pooled and 116 stored at 4°C. Protein concentration is estimated by its absorbance at 280 nm using the calculated extinction coefficient based on its amino acid sequence. The proteins ate refolded by diluting the sample slowly into freshly prepared refolding buffer consisting of: 20 mM Tris, pH 8.6, 0.3 M NaCl, 2.5 M urea, 5 mM cysteine, 20 mM glycine and 1 mM EDTA. Refolding volumes are chosen so that the final protein concentration is between 50 to 100 micrograms/ml. The refolding solution is stirred gently at 4°C for 12-36 hours. The refolding reaction is quenched by the addition of TFA to a final concentration of 0.4% (pH of approximately 3). Before further purification of Ihe protein, the solution is filtered through a 0.22 micron filter and acetonitrile is added to 2-10% final concentration. The refolded protein is chromatographed on a Poros Rl/H reversed phase column using a mobile buffer of 0.1% TFA with elution with a gradient of acetonitrile from 10 to 80%. Aliquots of fractions with A280 absorbance are analyzed on SDS polyaciylamide gels and fractions containing homogeneous refolded protein are pooled. Generally, the properly refolded species of most proteins are eluted at Ihe lowest concentrations of acetonitrile since those species are the most compact with their hydrophobic interiors shielded from interaction with the reversed phase resin. Aggregated species are usually eluted at higher acetonitrile concentrations, hi addition to resolving misfolded forms of proteins fiom the desired form, the reversed phase step also removes endotoxin from the samples. Fractions containing the desired folded TAT polypeptide are pooled and the acetonitrile removed using a gentle stream of nitrogen directed at the solution. Proteins are formulated into 20 mM Hepes, pH 6.8 with 0.14 M sodium chloride and 4% mannitol by dialysis or by gel filtration using G25 Superfine (Pharmacia) resins equilibrated in the formulation buffer and sterile filtered. Certain of the TAT polypeptides disclosed herein have been successfully expressed and purified using this technique(s). EXAMPLE 5: Expression of TAT in mammalian cells This example illustrates preparation of a potentially glycosylated form of TAT by recombinant expression in mammalian cells. The vector, pRK5 (see EP 307,247, published March 15,1989), is employed as the expression vector. Optionally, the TAT DHA is ligated into pRK5 with selected restriction enzymes to allow insertion of the TAT DNA using ligation methods such as described in Sambrook et al., supra. The resulting vector is called pRK5-TAT. In one embodiment, the selected host cells may be293 cells. Human293 cells (ATCC CCL 1573) are grown to confluence in tissue culture plates in medium such as DMEM supplemented with fetal calf serum and optionally, nutrient components and/or antibiotics. About 10 p,g pRK5-TAT DNA is mixed with about 1 pg DNA encoding the VA RNA gene [Thimmappaya et al., Cell. 31:543 (1982)] and dissolved in 500 |ilof 1 mM Tris-HCl, 0.1 mM EDTA, 0.227MCaCl2. To this mixture is added, dropwise, 500 p.1 of 50 mM HEPES (pH7.35),280mMNaCl, 1.5mM NaP04, and a precipitate is allowed tp form for 10 minutes at 25°C. The precipitate is suspended and added to the 293 cells and allowed to settle for about four hours at 37°C. The culture medium is aspirated off and 2 ml of 20% glycerol in PBS is added for 30 seconds. The 293 cells are then washed with serum free medium, fresh medium is added and the cells are incubated for about 5 days. 117 Approximately 24 hows after the transfections, Ihe culture medium is removed and replaced with culture medium (alone) or culture medium containing 200 pCi/ml 35S-cysteine and 200 (xCi/ml 35S-metbionine. After a 12 hour incubation, the conditioned medium is collected, concentrated on a spin filter, and loaded onto a 15% SDS gel. The processed gel may be dried and exposed to 151m for a selected period of time to reveal the presence of TAT polypqptide. The cultures containing transacted cells may undergo further incubation (in serum free medium) and die medium is tested in selected bioassays. In an alternative technique, TAT may be introduced into 293 cells transiently using the dextran sulfate method described by Somparyrac et al., Proc. Nafl. Acad. Sci.. 12:7575 (1981). 293 cells are grown to mnvimal density in a spinner flask and 700 jig pRK5-TAT DNA is added. The cells are first concentrated fiom the spinner flask by centrifugation and washed with PBS. The DNA-dextran precipitate is incubated on the cell pellet for four hours. The cells are treated with 20% glycerol for 90 seconds, washed with tissue culture medium, and reintroduced into the spinner flask containing tissue culture medium, 5 |xg/ml bovine insulin and 0.1 fig/ml bovine transferrin. After about four days, tide conditioned media is centrifiiged and filtered to remove cells and debris. The sample containing expressed TAT can then be concentrated and purified by any selected method, such as dialysis and/or column chromatography. In another embodiment, TAT can be expressed in CHO cells. The pRK5-TAT can be transfected into CHO cells using known reagents such as CaP04 or DEAE-dextran. As described above, the cell cultures can be incubated, and the medium replaced with culture medium (alone) or medium containing a radiolabel such as 35S-methionine. After detennining the presence of TAT polypqptide, the culture medium may be replaced with serum free medium. Preferably, the cultures are incubated for about 6 days, and then the conditioned medium is harvested. The medium containing the expressed TAT can then be concentrated and purified by any selected method. Epitope-tagged TAT may also be expressed in host CHO cells. The TAT may be subcloned out of the pRK5 vector. The subclone insert can undergo PCR to fuse in frame with a selected epitope tag such as a poly-his tag into a Baculovirus expression vector. The poly-his tagged TAT insert can then.be subcloned into a SV40 driven vector containing a selection marker such as DHFR for selection of stable clones. Finally, the CHO cells can be transfected (as described above) with the SV40 driven vector. Labeling may be performed, as described above, to verify expression. The culture medium containing the expressed poly-His tagged TAT can then be concentrated and purified by any selected method, such as by NP-chelate affinity chromatography. TAT may also be expressed in CHO and/or COS cells by a transient expression procedure or in CHO cells by another stable expression procedure. Stable expression in CHO cells is performed using the following procedure. The proteins are expressed as an IgO construct (immunoadhesin), in which the coding sequences for the soluble forms (e.g. extracellular domains) ofthe respective proteins are fused to an IgGl constant region sequence containing the hinge, CH2 and CH2 domains and/or is a poly-His tagged form. Following PCR amplification, the respective DNAs are subcloned in a CHO expression vector using standard techniques as described in Ausubel et al., Current Protocols of Molecular Biology. Unit 3.16, John Wiley and Sons (1997). CHO expression vectors are constructed to have compatible restriction sites 5' and 3' of the DNA 118 of interest to allow the convenient shuttling of cDNA's. The vector used expression in CHO cells is as described in Lucas et al., Nucl. Acids Res. 24:9 (1774-1779 (1996), and uses the SV40 early promoter/enhancer to drive expression of fee cDNA of interest and dihydrofolate reductase (DHFR). DHFR expression permits selection for stable maintenance of the plasmid following transfection. Twelve micrograms of the desired plasmid DNA is introduced into approximately 10 million CHO cells 5 using commercially available transfection reagents Superfect® (Quiagen), Dosper® or Fugene® (Boehringer Mannheim). The cells are grown as described in Lucas et al., supra. Approximately 3 x 107 cells are frozen in an ampule for further growth and production as described below. The ampules containing die plasmid DNA are thawed by placement into water bath and mixed by vortexing. The contents are pipetted into a centrifuge tube containing 10 mLs of media and centrifiiged at 1000 10 ipm for 5 minutes. The supernatant is aspirated and the cells are resuspended in 10 mL of selective media (0.2 fjm filtered PS20 with 5% 0.2 jum diafiltered fetal bovine serum). Hie cells are then aliquoted into a 100 mL spinner containing 90 mL of selective media. After 1-2 days, the cells are transferred into a250 mL spinner filled with 150 ' mL selective growth medium and incubated at 37°C. After another 2-3 days, 250 mL, 500 mL and2000 mL spinners are seeded with 3 x 105 cells/mL. The cell media is exchanged with fresh media by centrifugation and resuspension 15 in production medium. Although any suitable CHO media may be employed, a production medium described in U.S. Patent No. 5,122,469, issued June 16,1992 may actually be used. A 3L production spinner is seeded at 1.2 x 106 cells/mL. On day 0, the cell number pH ie determined. On day 1, the spinner is sampled and sparging with filtered air is commenced. On day 2, the spinner is sampled, die temperature shifted to 33 °C, and 30 mL of500 g/L glucose and 0,6 mL of 10% antifoam (e.g., 35% polydimethylsiloxane emulsion, Dow Coming 365 Medical Grade 20 Emulsion) taken. Throughout the production, the pH is adjusted as necessary to keep it at around 7.2. After 10 days, or until the viability dropped below 70%, die cell culture is harvested by centrifugation and filtering through a 0.22 /j.m filter. The filtrate was either stored at 4°C or immediately loaded onto columns for purification. For die poly-His tagged constructs, the proteins are purified using a Ni-NTA column (Qiagen). Before purification, imidazole is added to die conditioned media to a concentration of 5 mM. Hie conditioned media is 25 pumped onto a 6 ml Ni-NTA column equilibrated in 20 mMHepes, pH 7.4, buffer containing 0.3 MNaCl and 5 mM imidazole at a flow rate of 4-5 ml/min. at 4°C. After loading, die column is washed with additional equilibration buffer and the protein eluted with equilibration buffer containing 0.25 M imidazole. The highly purified protein is subsequendy desalted into a storage buffer containing 10 mM Hepes, 0.14 M NaCl and 4% mannitol, pH 6.8, with a 25 ml G25 Superfine (Pharmacia) column and stored at -80°C. 30 Immunoadhesin (Fc-containing) constructs are purified from the conditioned media as follows. The conditioned medium is pumped onto a 5 ml Protein A column (Pharmacia) which had been equilibrated in 20 mM Na phosphate buffer, pH 6.8. After loading, die column is washed extensively with equilibration buffer before elution with 100 mM citric acid, pH 3.5. Ihe eluted protein is immediately neutralized by collecting 1 ml fractions into tubes containing 275 jt/L of 1M Tris buffer, pH 9. The highly purified protein is subsequendy desalted into 35 storage buffer as described above for the poly-His tagged proteins. The homogeneity is. assessed by SDS polyacrylamide gels and by N-terminal amino acid sequencing by Edman degradation. 119 Certain of the TAT polypeptides disclosed herein have been successfully expressed and purified using this technique(s). EXAMPLE 6: Expression of TAT in Yeast The following method describes recombinant expression of TAT in yeast First, yeast expression vectors are constructed for intracellular production or secretion of TAT from the ADH2/GAPDH promoter. DNA encoding TAT and the promoter is inserted into suitable restriction enzyme sites in'thfe selected plasmid to direct intracellular expression of TAT. For secretion, DNA encoding TAT can be cloned into die selected plasmid, together with DNA encoding the ADH2/GAPDH promoter, a native TAT signal peptide or other mammalian signal peptide, or, for example, a yeast alpha-factor or invertase secretory signal/leader sequence, and linker sequences (if needed) for expression of TAT. Yeast cells, such as yeast strain AB110, can then be transformed with the expression plasmids described above and cultured in selected fermentation media. Hie transformed yeast supematants can be analyzed by precipitation with 10% trichloroacetic acid and separation by SDS-PAGE, followed by staining of the gels with Coomassie Blue stain. Recombinant TAT can subsequently be isolated and purified by removing the yeast cells from the fermentation medium by centrifugation and then concentrating the medium using selected cartridge filters. The concentrate containing TAT may further be purified using selected column chromatography resins. Certain of the TAT polypeptides disclosed herein have been successfully expressed and purified using this technique(s). EXAMPLE 7: Expression of TAT in Baculnvims-Tnfected Insect Cells The following method describes recombinant expression of TAT in Bac'ulovirus-infected insect cells. The sequence coding for TAT is fused upstream of an epitope tag contained within a baculovirus expression vector. Such epitope tags include poly-his tags and immunoglobulin tags (like Fc regions of IgG). A variety of plasmids may be employed, including plasmids derived from commercially available plasmids such as pVL1393 (Novagen). Briefly, the sequence encoding TAT or the desired portion ofthe coding sequence of TAT such as Ihe sequence encoding an extracellular domain of a transmembrane protein or the sequence encoding ihe mature protein if the protein is extracellular is amplified by PCR with primers complementary to the 5' and 3' regions. The 5' primer may incorporate flanking (selected) restriction enzyme sites. The product is then digested with those selected restriction enzymes and subcloned into the expression vector. Recombinant baculovirus is generated by co-transfecting the above plasmid and BaculoGold™ virus DNA (Pharmingen) into Spodoptera frugiperda ("Sf9") cells (ATCC CRL 1711) using lipofectin (commercially available from GIBCO-BRL). After 4-5 days of incubation at 28°C, the released viruses are harvested and used for further amplifications. Viral infection and protein expression are performed as described by O'Reilley et al., Baculovirus expression vectors: A Laboratory Manual Oxford: Oxford University Press (1994). Expressed poly-his tagged TAT can then be purified, for example, by Ni2+-chelate affinity chromatography as follows. Extracts are prepared from recombinant virus-infected Sf9 cells as described by Rupert et al., Nature. 120 362:175-179(1993). Briefly, Sf9 cells are washed, resuspended in sonication buffer (25 mLHepes, pH 7.9; 12.5 mM MgClj; 0.1 mM EDTA; 10% glycerol; 0.1% NP-40; 0.4 M KC1), and sonicated twice for 20 seconds on ice. The sonicates are cleared by centrifugation, and the supernatant is diluted 50-fold in loading buffer (50 mM phosphate, 300 mM NaCl, 10% glycerol, pH 7.8) and filtered through a 0.45 ptm filter. A NP-NTA agarose column (commercially available fiom Qiagen) is prepared with a bed volume of 5 mL, washed with 25 mL of water and equilibrated with 25 mL of loading buffer. The filtered cell extract is loaded onto the column at 0.5 mL per minute. The column is washed to baseline A280 with loading buffer, at which point fraction collection is started. Next, the " column is washed with a secondary wash buffer (50 mM phosphate; 300 mM NaCl, 10% glycerol, pH 6.0), which elutes nonspecifically bound protein. After reaching A^ baseline again, the column is developed with a 0 to 500 mM Imidazole gradient in the secondary wash buffer. One mL fiactions are collected and analyzed by SDS-PAOE and silver staining or Western blot with Ni2+-NTA-conjugated to alkaline phosphatase (Qiagen). Fractions containing the eluted His,0-tagged TAT are pooled and dialyzed against loading buffer. Alternatively, purification of the IgG tagged (or Fc tagged) TAT can be performed using known chromatography techniques, including for instance, Protein A or protein G column chromatography. Certain of Ihe TAT polypeptides disclosed herein have been successfully expressed and purified using fhistechnique(s). KXAMPT.K 8: Preparation of Antibodies that Bind TAT This example illustrates preparation of monoclonal antibodies which can specifically bind TAT. Techniques for producing the monoclonal antibodies are known in the art and are described, for instance, in Goding, supra. Immunogens that may be employed include purified TAT, fusion proteins containing TAT, and cells expressing recombinant TAT on the cell surfece. Selection of the immunogen can be made by the skilled artisan without undue experimentation. Mice, such as Balb/c, are immunized with the TAT immunogen emulsified in complete Freund's adjuvant and injected subcutaneously or intraperitoneally in an amount from 1-100 micrograms. Alternatively, the immunogen is emulsified in MPL-TDM adjuvant (Ribi Immunochemical Research, Hamilton, MT) and injected into the animal's hind foot pads. The immunized mice are then boosted 10 to 12 days later with additional immunogen emulsified in the selected adjuvant Thereafter, for several weeks, Ihe mice may also be boosted with additional immunization injections. Serum samples may be periodically obtained from Ihe mice by retro-orbital bleeding for testing in ELISA assays to detect anti-TAT antibodies. After a suitable antibody titer has been detected, the animals "positive" for antibodies can be injected with a final intravenous injection of TAT. Three to four days later, the mice are sacrificed and the spleen cells are harvested. The spleen cells are then fused (using 35% polyethylene glycol) to a selected murine myeloma cell line such as P3X63AgU.l, available from ATCC, No. CRL 1597. The fusions generate hybridoma cells which can then be plated in 96 well tissue culture plates containing HAT (hypoxantbine, aminopterin, and thymidine) medium to inhibit proliferation of non-fused cells, myeloma hybrids, and spleen cell hybrids. The hybridoma cells will be screened in an ELISA for reactivity against TAT. Determination of "positive" hybridoma ceils secreting the desired monoclonal antibodies against TAT is within the skill in the art 121 The positive hybridoma cells can be injected intraperitoneally into syngeneic Balb/c mice to produce ascites containing Hie anti-TAT monoclonal antibodies. Alternatively, the hybridoma cells can be grown in tissue culture flasks or roller bottles. Purification of the monoclonal antibodies produced in the ascites can be accomplished using ammonium sul&te precipitation, followed by gel exclusion chromatography. Alternatively, affinity chromatography based upon binding of antibody to protein A or protein G can be employed. TOTAMPTK 9: Purification of TAT Polypeptides Using Specific Antibodies Native or recombinant TAT polypeptides may be purified by a variety of standard techniques in the art of protein purification For example, pro-TAT polypeptide, mature TAT polypeptide, or pre-TAT polypeptide is purified by immunoaffinity chromatography using antibodies specific for the TAT polypeptide of interest. In general, an immunoaffinity column is constructed by covalently coupling the anti-TAT polypeptide antibody to an activated chromatographic resin. Polyclonal immunoglobulins are prepared fiom immune sera either by precipitation with ammonium sulfate or by purification on immobilized Protein A (Pharmacia LKB Biotechnology, Piscataway, NJ.). Likewise, monoclonal antibodies are prepared from mouse ascites fluid by ammonium sulfate precipitation or chromatography on immobilized Protein A. Partially purified immunoglobulin is covalently attached to a chromatographic resin such as CnBr-activated SEPHAROSE™ (Pharmacia LKB Biotechnology). Hie antibody is coupled to the resin, the resin is blocked, and the derivative resin is washed according to the manufacturer's instructions. Such an immunoaffinity column is utilized in the purification of TAT polypeptide by preparing a fraction from cells containing TAT polypeptide in a soluble form. This preparation is derived by solubilization of the whole cell or of a subcellular fraction obtained via differential centrifugation by the addition of detergent or by other methods well known in the art Alternatively, soluble TAT polypeptide containing a signal sequence may be secreted in useful quantity into the medium in which the cells are grown. A soluble TAT polypeptide-containing preparation is passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of TAT polypeptide (e.g., high ionic strength buffers in the presence of detergent). Then, the column is eluted under conditions that disrupt antibody/TAT polypeptide binding (e.g., a low pH buffer such as approximately pH 2-3, or a high concentration of a chaotrope such as urea or thiocyanate ion), and TAT polypeptide is collected. EXAMPLE 10: In Vitro Tumor Cell tailing Assay Mammalian cells expressing the TAT polypeptide of interest may be obtained using standard expression vector and cloning techniques. Alternatively, many tumor cell lines expressing TAT polypeptides of interest are publicly available, for example, through the ATCC and can be routinely identified using standard ELISA or FACS analysis. Anti-TAT polypeptide monoclonal antibodies (and toxin conjugated derivatives thereof) may then be employed in assays to determine the ability of the antibody to kill TAT polypeptide expressing cells in vitro. For example, cells expressing the TAT polypeptide of interest are obtained as described above and plated into 96 well dishes. In one analysis, the antibody/toxin conjugate (or naked antibody) is included throughout the 122 cell incubation for a period of 4 days. Id a second independent analysis, the cells arc incubated for 1 hour with the antibody/toxin conjugate (or naked antibody) and then washed and incubated in Ihe absence of antibody/toxin conjugate for a period of 4 days. Cell viability is then measured wing the CellHter-Glo Luminescent Cell Viability Assay fiom Promega (Cat# G7571). Untreated cells serve as a negative control. EXAMPLE 11: In Vivo Tumor Cell Killing Assay To test file efficacy of conjugated or unconjugated anti-TAT polypeptide monoclonal antibodies, anti-TAT antibody is injected intraperitoneally into nude mice 24 hours prior to receiving tumor promoting cells subcutaneously in the flank. Antibody injections continue twice per week for the remainder of the study. Tumor volume is then measured twice per week. Deposit of Material The following materials have been deposited with the American Type Culture Collection, 10801 University Blvd., Manassas, VA 20110-2209, USA (ATCC): Table 7 Material ATCC Dep. No. Deposit Date DNA64888-1542 203249 September 9, 1998 DNA64889-1541 203250 September 9, 1998 DNA57700-1408 203583 January 12,1999 These deposits were made under Ihe provisions of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purpose of Patent Procedure and the Regulations thereunder (Budapest i Treaty). This assures maintenance of a viable culture of the deposit for 30 years fiom the date of deposit The deposits will be made available by ATCC under the terms of the Budapest Treaty, and subject to an agreement between Genentech, Inc. and ATCC, which assures permanent and unrestricted availability of the progeny of the culture of the deposit to the public upon issuance of the pertinent U.S. patent or upon laying open to the public of any U.S. or foreign patent application, whichever comes first, and assures availability of the progeny to one determined by the U.S. Commissioner of Patents and Trademarks to be entitled thereto according to 35 USC § 122 and the Commissioner's rules pursuant thereto (including 37 CFR § 1.14 with particular reference to 886 OG 638). The assignee of the present application has agreed that if a culture of the materials on deposit should die or be lost or destroyed when cultivated under suitable conditions, the materials will be promptly replaced on notification With another of the same. Availability of the deposited material is not to be construed as a license to practice the invention in contravention of the rights granted under the authority of any government in accordance with its patent laws. The foregoing written specification is considered to be sufficient to enable one skilled in the art to practice the invention. The present invention is not to be limited in scope by the construct deposited, since the deposited embodiment is intended as a single illustration of certain aspects of the invention and any constructs that are fimctionally equivalent are within the scope of this invention. Ihe deposit of material herein does not 123 constitute an admission that the written description herein contained is inadequate to enable Ihe practice of any aspect of the invention, including the best mode thereof nor is it to be construed as limiting the scope of the claims to the specific illustrations that it represents. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art fiom the foregoing description and Ml within the scope of the appended claims. 124 <1 </div>

Claims

<div class="application article clearfix printTableText" id="claims"> WHAT IS CLAIMED IS:

1. A method of inhibiting the growth of an isolated or non-human cancer cell that expresses a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); 5 (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; 10 (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), said method comprising contacting said cell with an antibody, TAT binding oligopeptide or TAT binding organic molecule that binds to said protein, the binding of said antibody, oligopeptide or organic molecule to said protein thereby causing an inhibition of growth of said cell. 15

2. A method of Claim 1, wherein said antibody is a monoclonal antibody.

3. A method of Claim 1, wherein said antibody is an antibody fragment. 20

4. A method of Claim 1, wherein said antibody is a chimeric or a humanized antibody.

5. A method of Claim 1, wherein said antibody, oligopeptide or organic molecule is conjugated to a growth inhibitory agent. 25

6. A method of Claim 1, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent.

7. A method of Claim 6, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes. 30

8. A method of Claim 6, wherein the cytotoxic agent is a toxin.

9. A method of Claim 8, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin. 35

10. A method of Claim 8, wherein the toxin is a maytansinoid.

11. A method of Claim 1, wherein said antibody is produced in bacteria. 40

12. A method of Claim 1, wherein said antibody is produced in CHO cells.

13. A method of Claim 1, wherein said cancer cell is further exposed to radiation treatment or a chemotherapeutic agent. 629984-1 125 I OFFICE H SEP 2007 5 10 15 20 25 30 35 40 45

14. A method of Claim 1, wherein said cancer cell is selected from the group consisting of a breast cancer cell, a colorectal cancer cell, a lung cancer cell, an ovarian cancer cell, a central nervous system cancer cell, a liver cancer cell, a bladder cancer cell, a pancreatic cancer cell, a cervical cancer cell, a melanoma cell and a leukaemia cell.

15. A method of Claim 1, wherein said protein is more abundantly expressed by said cancer cell as compared to a normal cell of the same tissue origin.

16. A method of Claim 1 which causes the death of said cell.

17. A method of Claim 1, wherein said protein has: (a) the amino acid sequence shown in Figure 6 (SEQ ID NO:6); (b) the amino acid sequence shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3).

18. A method of determining the presence of a protein in a sample suspected of containing said protein, wherein said protein has at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3, said method comprising exposing said sample to an antibody, TAT binding oligopeptide or TAT binding organic molecule that binds to said protein and determining binding of said antibody, oligopeptide or organic molecule to said protein in said sample, wherein binding of the antibody, oligopeptide or organic molecule to said protein is indicative of the presence of said protein in said sample.

19. A method of Claim 18, wherein said antibody is a monoclonal antibody.

20. A method of Claim 18, wherein said antibody is an antibody fragment.

21. A method of Claim 18, wherein said antibody is a chimeric or a humanized antibody.

22. A method of Claim 18, wherein said antibody is produced in bacteria. 10 20 25 30 35 40

23. A method of Claim 18, wherein said antibody is produced in CHO cells.

24. A method of Claim 18, wherein said sample is a cell containing sample and the cell is a cancer cell.

25. A method of Claim 24, wherein said cancer cell is selected from the group consisting of a breast cancer cell, a colorectral cancer cell, a lung cancer cell, an ovarian cancer cell, a central nervous system cancer cell, a liver cancer cell, a bladder cancer cell, a pancreatic cancer cell, a cervical cancer cell, a melanoma cell and a leukaemia cell.

26. A method of Claim 24, wherein said protein is more abundantly expressed by said cancer cell as compared to a normal cell of the same tissue origin.

27. A method of Claim 18, wherein said sample comprises a cell suspected of expressing said protein.

28. A method of Claim 18, wherein said antibody, oligopeptide or organic molecule is detectably labeled.

29. A method of Claim 18, wherein said protein has: (a) the amino acid sequence shown in Figure 6 (SEQ ID NO:6); (b) the amino acid sequence shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3).

30. A method of diagnosing the presence of a tumor in a mammal, said method comprising determining the level of expression of a gene encoding a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in any one of Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); or 629984-1 127 (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in a test sample of tissue cells obtained from said mammal and in a control sample of known normal cells of the same tissue origin, wherein a higher level of expression of said protein in the test sample, as compared to the control sample, is indicative of the presence of tumor in 5 the mammal from which the test sample was obtained.

31. A method of Claim 30, wherein the step of determining the level of expression of a gene encoding said protein comprises employing an oligonucleotide in an in situ hybridization or RT-PCR analysis. 10

32. A method of Claim 30, wherein the step determining the level of expression of a gene encoding said protein comprises employing an antibody in an immunohistochemistry or Western blot analysis. 15

33. A method of Claim 30, wherein said protein has: (a) the amino acid sequence shown in Figure 6 (SEQ ID NO:6); (b) the amino acid sequence shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in any one of 20 Figure 6 (SEQ ID NO:6), with its associated signal peptide sequence; (d) an amino acid sequence of an extracellular domain of the polypeptide shown in any one of Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); or 25 (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3).

34. A method of diagnosing the presence of a tumor in a mammal, said method comprising contacting a test sample of tissue cells obtained from said mammal with an antibody, 30 oligopeptide or organic molecule that binds to a protein having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its 35 associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); or (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in 40 Figure 3 (SEQ ID NO:3), and detecting the formation of a complex between said antibody, TAT binding oligopeptide or TAT binding organic molecule and said protein in the test sample, wherein the formation of a complex is indicative of the presence of a tumor in said mammal.

35. A method of Claim 34, wherein said antibody, oligopeptide or organic molecule is 45 detectably labeled. \ i, SEP 629984-1 128 RECE1VJ_P

36. A method of Claim 34, wherein said test sample of tissue cells is obtained from an individual suspected of having a cancerous tumor.

37. A method of Claim 34, wherein said protein has: 5 (a) the amino acid sequence shown in Figure 6 (SEQ ID NO:6); (b) the amino acid sequence shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (c) an amino acid sequence of an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide sequence; 10 (d) an amino acid sequence of an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide sequence; (e) an amino acid sequence encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); or (f) an amino acid sequence encoded by the full-length coding region of the nucleotide sequence 15 shown in Figure 3 (SEQ ID NO:3).

38. Use of a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 20

39. Use of a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for treating a tumor.

40. Use of a nucleic acid having at least 80% sequence identity to the nucleotide sequence 25 shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for treatment or prevention of a cell proliferative disorder.

41. Use of an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a 30 medicament for the therapeutic treatment or diagnostic detection of a cancer.

42. Use of an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of medicament for treating a tumor. 35

43. Use of a host cell comprising an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer. 40

44. Use of a host cell comprising an expression vector comprising a nucleic acid having at least 80% sequence identity to the nucleotide sequence shown in Figure 3 (SEQ ID NO:3) in the preparation of a medicament for treating a tumor. 629984-1 129 ■™gs&rsrr' \ i, SEP 2™>?

45. Use of a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its 5 associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of nucleotide sequence shown in 10 Figure 3 (SEQ ID NO:3), in the preparation of a medicament for the therapeutic treatment or diagnostic detection of a cancer.

46. Use of a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); 15 (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; 20 (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for treating a tumor.

47. Use of an antibody, oligopeptide or TAT binding organic molecule that binds a 25 polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO: 6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; 30 (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for the therapeutic treatment or 35 diagnostic detection of a cancer.

48. A use of Claim 47, wherein said antibody is a monoclonal antibody.

49. A use of Claim 47, wherein said antibody is a antibody fragment. 40

50. A use of Claim 47, wherein said antibody is a chimeric or a humanized antibody.

51. A use of Claim 47, wherein said antibody, oligopeptide or organic molecule is conjugated to a growth inhibitory agent. 45 5 10 15 20 25 30 35 40 45

52. A use of Claim 47, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent.

53. A use of Claim 52, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes

54. A use of Claim 52, wherein the cytotoxic agent is a toxin.

55. A use of Claim 54, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin.

56. A use of Claim 54, wherein the toxin is a maytansinoid

57. A use of Claim 47, wherein said antibody is produced in bacteria

58. A use of Claim 47, wherein said antibody is produced in CHO cells.

59. A use of an antibody, oligopeptide or TAT binding organic molecule that binds a polypeptide having at least 80% amino acid sequence identity to: (a) the polypeptide shown in Figure 6 (SEQ ID NO:6); (b) the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (c) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), with its associated signal peptide; (d) an extracellular domain of the polypeptide shown in Figure 6 (SEQ ID NO:6), lacking its associated signal peptide; (e) a polypeptide encoded by the nucleotide sequence shown in Figure 3 (SEQ ID NO:3); (f) a polypeptide encoded by the full-length coding region of the nucleotide sequence shown in Figure 3 (SEQ ID NO:3), in the preparation of a medicament for treating a tumor.

60. A use of Claim 59, wherein said antibody is a monoclonal antibody.

61. A use of Claim 59, wherein said antibody is an antibody fragment.

62. A use of Claim 59, wherein said antibody is a chimeric or a humanized antibody.

63. A use of Claim 59, wherein said antibody, oligopeptide or organic molecule is conjugated to a growth inhibitory agent.

64. A use of Claim 59, wherein said antibody, oligopeptide or organic molecule is conjugated to a cytotoxic agent.

65. A use of Claim 64, wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.

66. A use of Claim 64, wherein the cytotoxic agent is a toxin. 629984-1 131

67. A use of Claim 66, wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin.

68. A use of Claim 66, wherein the toxin is a maytansinoid. 5

69. A use of Claim 59, wherein said antibody is produced in bacteria.

70. A use of Claim 59, wherein said antibody is produced in CHO cells. 10

71. A method of any one of Claims 1, 18, 30 or 34, substantially as herein described with reference to any example thereof.

72. A use of any one of Claims 38 to 47, or 59, substantially as herein described with reference to any example thereof. 15 629984-1 132 intellectual property office of n.z i 14 SEP 2007 I -■-/>ci\i c=r>i </div>