Tumor necrosis factor related ligand
View Patent ↗The present invention relates to Tumor Necrosis Factor Related Ligand (TRELL), a novel member of the tumor necrosis factor family (TNF), modified TRELL, and pharmaceutical compositions comprising them.
1. A substantially pure polypeptide comprising amino acids 36 to 284 of SEQ ID NO: 4.
2. A substantially pure polypeptide consisting essentially of amino acids 36 to 284 of SEQ ID NO: 4.
3. A substantially pure polypeptide that comprises a soluble fragment of SEQ ID NO:4, wherein said fragment is capable of binding to and inducing apoptosis in an HT29 colon carcinoma cell.
4. A substantially pure polypeptide comprising SEQ ID NO: 2.
5. A substantially pure polypeptide consisting essentially of SEQ ID NO: 2.
6. A substantially pure polypeptide that comprises a soluble fragment of SEQ ID NO:2, wherein the fragment is capable of binding to and inducing apoptosis in an HT-29 colon carcinoma cell and, wherein the amino terminus of the polypeptide is at any one of amino acids 22 to 80 of SEQ ID NO: 2.
7. A substantially pure polypeptide comprising an amino acid sequence encoded by a nucleic acid sequence that hybridizes under high stringency conditions to the complement of a coding sequence, wherein the stringent conditions comprise washing steps using 2×SSC, 0.1% SDS at 65° C., wherein said amino acid sequence is capable of binding to and inducing apoptosis in an HT-29 colon carcinoma cell, and wherein said coding sequence is selected from the group consisting of:
(a) SEQ ID NO: 1; and
(b) nucleotides 65 to 676 of SEQ ID NO: 1.
8. A substantially pure polypeptide comprising an amino acid sequence encoded by a nucleic acid sequence that hybridizes under high stringency conditions to the complement of a coding sequence, wherein the stringent conditions comprise washing steps using 2×SSC, 0.1% SDS at 65° C., wherein said amino acid sequence is capable of binding to and inducing apoptosis in an HT-29 colon carcinoma cell, and wherein said coding sequence is selected from the group consisting of:
(a) nucleotides 106 to 852 of SEQ ID NO: 3; and
(b) nucleotides 241 to 852 of SEQ ID NO: 3.
9. The substantially pure polypeptide of claim 3 , wherein the amino terminus of the soluble fragment is at any one of amino acids 81 to 139 of SEQ ID NO: 4.
10. A composition comprising the polypeptide according to any one of claims 1 , 2 , 9 , 4 , 5 , 6 , 7 , 8 and 3 , and a pharmaceutically acceptable carrier.