TAT- 001 and methods of assessing and treating cancer
Surprisingly, the present inventors have discovered that expression of TAT-001 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-001 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-001 expression or activity, comprising: contacting a candidate compound with a TAT-001 and detecting the presence or absence of binding between said compound and said TAT-001, or detecting a change in TAT-001 expression or activity. Methods are also included for the identification of anti-cancer compounds and compounds that modulate TAT-001 expression or activity, comprising: administering a compound to a cell or cell population, and detecting a change in TAT-001 expression or activity.
1 . A TAT-001 polypeptide, or fragment thereof, conjugated to an immunogenic carrier.
2 . The TAT-001 polypeptide claim 1 , wherein said immunogenic carrier is serum albumin, keyhole limpet hemocyanin, soybean trypsin inhibitor, or bovine thyroglobulin.
3 . The TAT-001 polypeptide of claim 1 , wherein said polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 1, 3, 5, or 8.
4 . The TAT-001 polypeptide of claim 3 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NOs: 1, 3, 5, or 8.
5 . A composition comprising a TAT-001 polypeptide, or fragment thereof, and an adjuvant.
6 . The composition of claim 5 , wherein said adjuvant is selected from the group consisting of Freund's adjuvant, aluminum salts, saponins, triterpenes, monophosphoryl lipid A, cholera toxin, ISCOM'S®, PROVAX®, DETOX®, SAF, Alum®, and Saponin®.
7 . The composition of claim 5 , wherein said polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 1, 3, 5, or 8.
8 . The composition of claim 7 , wherein said polypeptide comprises the amino acid sequence SEQ ID NOs: 1, 3, 5, or 8.
9 . A method of making an antibody that specifically binds to a TAT-001 polypeptide, said method comprising the steps of:
(i) immunizing a mammal with a TAT-001 polypeptide or immunogenic fragment thereof;
(ii) textracting splenocytes from the immunized mammal;
(iii) producing a hybridoma cell line by fusing said splenocytes with a myeloma cell line; and
(iv) purifying an antibody from said hybridoma cell line.
10 . The method of claim 9 , wherein said TAT-001 polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 1, 3, 5, or8.
11 . The method of claim 10 , wherein said TAT-001 polypeptide comprises the amino acid sequence SEQ ID NOs: 1, 3, 5, or 8.
12 . The method of claim 9 , wherein said immunizing of step (i) further comprises administering an adjuvant to said mammal.
13 . The method of claim 9 , wherein said mammal is a mouse.
14 . An antibody or antibody fragment that specifically binds to a TAT-001 polypeptide, or fragment thereof, produced by the method of claim 9 .
15 . The antibody of claim 14 , wherein said antibody or antibody fragment is humanized.
16 . A method of making a TAT-001 polypeptide, or fragment thereof, said method comprising:
(i) introducing a TAT-001 nucleic acid into an isolated host cell;
(ii) incubating said host cell under conditions such that said TAT-001 polypeptide is expressed in the host cell; and
(iii) recovering said TAT-001 polypeptide from the host cell.
17 . The method of claim 16 , wherein said TAT-001 nucleic acid molecule encodes a polypeptide comprising an amino sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 1, 3, 5, or 8.
18 . The method of claim 17 , wherein said TAT-001 nucleic acid molecule encodes a polypeptide comprising the amino acid sequence of SEQ ID NOs: 1, 3, 5, or 8.
19 . The method of claim 16 , wherein said TAT-001 nucleic acid molecule comprises a nucleotide sequence that is at least 90% identical to the nucleotide sequence of SEQ ID NOs: 2, 4, or 6.
20 . The method of claim 19 , wherein said TAT-001 nucleic acid molecule comprises the sequence of SEQ ID NOs: 2, 4, or 6.