Tat-005 and Methods of Assessing and Treating Cancer
Surprisingly, the present inventors have discovered that expression of TAT-005 protein in human patients is associated with cancer, and that the over-expressed protein is present in plasma membrane fractions. Thus, the present inventors have discovered that TAT-005 is associated with abnormal development and growth, and may be useful as a target for the identification of anti-cancer com\ pounds, including antibodies for use in immunotherapy. Accordingly, the present invention provides methods for the identification of compounds that inhibit TAT-005 expression or activity, comprising: contacting a candidate compound with a TAT-005 and detecting the presence or absence of binding between said compound and said TAT-005, or detecting a change in TAT-005 expression or activity. Methods are also included for the identification of compounds that modulate TAT-005 expression or activity, comprising: administering a compound to a cell or cell population, and detecting a change in TAT-005 expression or activity. The methods of the invention are useful for the identification of anti-cancer compounds.
1 - 83 . (canceled)
84 . An antibody or antibody fragment that specifically binds to a TAT-005 polypeptide, or fragment thereof.
85 . The antibody of claim 84 , wherein said polypeptide comprises an amino acid sequence having at least 90% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
86 . The antibody of claim 84 , wherein said polypeptide comprises an amino acid sequence having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
87 . The antibody of claim 84 , wherein said polypeptide comprises an amino acid sequence having at least 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
88 . The antibody of claim 84 , wherein said polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
89 . The antibody of claim 84 , wherein said polypeptide consists of an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
90 . The antibody of claim 84 , 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.
91 . The antibody fragment of claim 84 , wherein said antibody fragment is a Fab fragment, an F(ab)′ 2 fragment, or an Fv fragment.
92 . The antibody of claim 84 , 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.
93 . The antibody of claim 84 , wherein said polypeptide or fragment thereof is present in association with a cellular membrane of a cancer cell at a relative level greater than with a non-cancer cell.
94 . The antibody of claim 94 , wherein said cancer cell is a colon cancer cell.
95 . A pharmaceutical composition comprising (i) a compound that binds to a TAT-005 polypeptide and (ii) a pharmaceutically acceptable carrier.
96 . The composition of claim 95 , wherein said compound is an antibody or fragment thereof that specifically binds to said TAT-005 polypeptide or fragment thereof.
97 . The composition of claim 96 , wherein said wherein said polypeptide comprises an amino acid sequence having at least 90% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
98 . The composition of claim 97 , wherein said wherein said polypeptide comprises an amino acid sequence having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
99 . The composition of claim 98 , wherein said wherein said polypeptide comprises an amino acid sequence having at least 99% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
100 . A method of detecting the presence of a TAT-005 polypeptide or fragment thereof in a sample, said method comprising contacting said sample with a TAT-005 binding molecule that specifically binds to a TAT-005 polypeptide or fragment thereof and assaying for binding of said molecule to said polypeptide or said fragment.
101 . The method of claim 100 , wherein said TAT-005 binding molecule is antibody or antibody fragment.
102 . The method of claim 100 , wherein said TAT-005 polypeptide or fragment thereof an amino acid sequence having at least 90% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21.
103 . The method of claim 100 , wherein said TAT-005 polypeptide or fragment thereof an amino acid sequence having at least 95% identity to an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 3, 6, 9, 12, 15, 18, and 21 .