TAT-031 and methods of assessing and treating cancer
Surprisingly, the present inventors have discovered that expression of TAT-031 protein in human patients is associated with cancer, and that the overexpressed protein is present in plasma membrane fractions. Thus, the present inventors have discovered that TAT-031 is associated with abnormal development and growth, and may be useful as a target for the identification of anti-cancer compounds, including antibodies for use in immunotherapy. Accordingly, the present invention provides methods for the identification of compounds that inhibit TAT-031 expression or activity, comprising: contacting a candidate compound with a TAT-031 and detecting the presence or absence of binding between said compound and said TAT-031, or detecting a change in TAT-031 expression or activity. Methods are also included for the identification of compounds that modulate TAT-031 expression or activity, comprising: administering a compound to a cell or cell population, and detecting a change in TAT-031 expression or activity. The methods of the invention are useful for the identification of anti-cancer compounds.
1 . An antibody or fragment thereof that specifically binds to a TAT-031 polypeptide.
2 . The antibody of claim 1 , wherein said polypeptide comprises the amino acid sequence of any of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 50-53, 61, 68, 70, 72, and 74.
3 . The antibody of claim 1 , wherein said antibody is a monoclonal antibody, a polyclonal antibody, a single-chain antibody, a chimeric antibody, a humanized antibody, a fully-humanized antibody, a human antibody, or a bispecific antibody.
4 . The antibody fragment of claim 1 , wherein said antibody fragment is a Fab fragment, an F(ab)′ 2 fragment, or an Fv fragment.
5 . The antibody of claim 1 , wherein said antibody is conjugated to a therapeutic moiety, a detectable label, a second antibody or a fragment thereof, a cytotoxic agent or a cytokine.
6 . A method of diagnosing an increased likelihood of developing a TAT-031-related disease or condition in a test subject, said method comprising analyzing nucleic acid molecules of the test subject to determine whether said test subject contains a mutation in a TAT-031 gene, wherein the presence of said mutation is an indication that said test subject has an increased likelihood of developing a TAT-031-related disease.
7 . The method of claim 6 , further comprising the step of using nucleic acid molecule primers specific for the TAT-031 gene for nucleic acid molecule amplification by the polymerase chain reaction.
8 . The method of claim 7 , further comprising the step of sequencing TAT-031 nucleic acid molecules from said test subject.
9 . The method of claim 6 , wherein said test subject is a mammal.
10 . The method of claim 9 , wherein said test subject is human.
11 . The method of claim 6 , wherein said analyzing is carried out by restriction fragment length polymorphism (RFLP) analysis.
12 . The method of claim 6 , wherein said disease or condition is a cellular proliferative disease.
13 . The method of claim 12 , wherein said cellular proliferative disease is cancer.
14 . The method of claim 13 , wherein said cancer is lung cancer.
15 . A probe for analyzing the TAT-031 nucleic acid molecules of an animal, said probe having at least 60% nucleic acid sequence identity to a sequence encoding a TAT-031 polypeptide or a fragment thereof, wherein said fragment encodes at least six contiguous amino acids and said probe hybridizes under high stringency conditions to at least a portion of a TAT-031 nucleic acid molecule.
16 . A method of detecting the presence of a TAT-031 nucleic acid in a sample, said method comprising contacting said sample with a probe of claim 15 .
17 . A kit for the analysis of a TAT-031 nucleic acid molecule, said kit comprising a nucleic acid molecule probe of claim 15 for analyzing the nucleic acid molecules of a test subject.
18 . A method of detecting the presence of a TAT-031 polypeptide in a sample, said method comprising contacting said sample with a TAT-031 binding molecule that specifically binds to a TAT-031 polypeptide and assaying for binding of said molecule to said polypeptide.
19 . A method of detecting the presence of a mutant TAT-031 polypeptide in a sample, said method comprising contacting said sample with an antibody that specifically binds to a mutant TAT-031 polypeptide and assaying for binding of said antibody to said mutant polypeptide.
20 . A kit for the analysis of a TAT-031 polypeptide, said kit comprising an antibody for analyzing the TAT-031 polypeptide of a test subject.
21 . A method for preventing or ameliorating the effect of a TAT-031 deficiency, said method comprising administering to a subject having a TAT-031 deficiency a therapeutically-effective amount of a compound to prevent or ameliorate said effect of said TAT-031 deficiency.
22 . The method of claim 21 , wherein said compound comprises a functional TAT-031 polypeptide.
23 . A method for preventing or ameliorating the effect of a TAT-031 polypeptide excess, said method comprising administering a therapeutically-effective amount of a compound to a subject having a TAT-031 excess, wherein said compound is sufficient to prevent or ameliorate said effect of said TAT-031 polypeptide excess.
24 . The method of claim 23 , wherein said TAT-031 excess is caused by a cellular proliferative disorder.
25 . The method of claim 24 , wherein said cellular proliferative disorder is cancer.
26 . The method of claim 25 , wherein said cancer is lung cancer.
27 . The method of claim 23 , wherein said compound is an antibody or fragment thereof which binds to a TAT-031 polypeptide.
28 . A substantially pure TAT-031 polypeptide or fragment thereof.
29 . A substantially pure nucleic acid molecule comprising a sequence encoding a TAT-031 polypeptide, or fragment thereof.
30 . A vector comprising the nucleic acid molecule of claim 29 .
31 . A cell comprising the vector of claim 30 .
32 . A non-human transgenic animal comprising the nucleic acid molecule of claim 29 .
33 . A composition for inducing an immune response in a subject, said composition comprising a substantially pure TAT-031 polypeptide or fragment thereof in a pharmaceutically-acceptable carrier.
34 . A composition for inducing an immune response in a subject, said composition comprising the nucleic acid molecule of claim 29 and a pharmaceutically-acceptable carrier.
35 . A method of inducing an immune response to a TAT-031 polypeptide, said method comprising the steps of:
(a) providing a TAT-031 polypeptide; and
(b) contacting said polypeptide with an immune system cell, thereby inducing an immune response to said polypeptide.
36 . A method of inducing an immune response in a subject comprising administering to said subject a composition comprising a TAT-031 polypeptide.
37 . A method of inducing an immune response in a subject comprising administering to said subject a composition comprising the nucleic acid molecule of claim 29 .
38 . A pharmaceutical composition comprising (i) a TAT-031 polypeptide and (ii) a pharmaceutically acceptable carrier.
39 . A method of preventing or treating a cellular proliferative disease in a subject comprising administering to said subject the pharmaceutical composition of claim 38 .
40 . A pharmaceutical composition comprising (i) a compound that binds to a TAT-031 polypeptide and (ii) a pharmaceutically acceptable carrier.
41 . The composition of claim 40 , wherein said compound is an antibody or fragment thereof that binds to said TAT-031 polypeptide.
42 . A method of preventing or treating a cellular proliferative disease in a subject patient, said method comprising administering to said subject the pharmaceutical composition of claim 40 .
43 . A pharmaceutical composition comprising (i) a TAT-031 nucleic acid molecule and (ii) a pharmaceutically acceptable carrier.
44 . A method of preventing or treating a cellular proliferative disease in a subject patient, said method comprising administering to said subject the pharmaceutical composition of claim 43.