Method of using a cytokine that induces apoptosis
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Abstract
A novel cytokine designated TRAIL induces apoptosis of certain target cells, including cancer cells and virally infected cells. Isolated DNA sequences encoding TRAIL are disclosed, along with expression vectors and transformed host cells useful in producing TRAIL polypeptides. Antibodies that specifically bind TRAIL are provided as well.
14 Citations
101 Claims
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1-28. -28. (canceled)
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29. A method of inducing death of cancer cells, comprising contacting TRAIL-sensitive cancer cells with TRAIL polypeptide, wherein said polypeptide comprises an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of amino acids 1 to 281 of SEQ ID NO:
- 2 and amino acids 1 to 291 of SEQ ID NO;
6, wherein said TRAIL polypeptide is capable of inducing apoptosis of Jurkat cells. - View Dependent Claims (31)
- 2 and amino acids 1 to 291 of SEQ ID NO;
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30. A method of inducing death of cancer cells, comprising contracting TRAIL-sensitive cancer cells with an oligomer comprising at least two soluble TRAIL polypeptides, wherein each of said soluble TRAIL polypeptides comprises an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of:
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a) the extracellular domain of human TRAIL (amino acids 39 to 281 of SEQ ID NO;
2); and
b) a fragment of said extracellular domain;
wherein said oligomer is capable of inducing apoptosis of Jurkat cells. - View Dependent Claims (47, 48, 49, 50, 54, 55, 56, 57, 59, 60, 61, 62, 66, 67, 71, 75)
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32. A method of inducing death of cancer cells, comprising contacting TRAIL-sensitive cancer cells with a soluble polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of:
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a) the extracellular domain of human TRAIL (amino acids 39 to 281 of SEQ ID NO;
2); and
b) a fragment of said extracellular domain;
wherein said polypeptide is capable of inducing apoptosis of Jurkat cells. - View Dependent Claims (33, 34, 35, 36, 42, 43, 72)
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37. A method of inducing death of cancer cells, comprising contacting TRAIL-sensitive cancer cells with a polypeptide that comprises a fragment of the human TRAIL protein of SEQ ID NO:
- 2, wherein said fragment kills TRAIL-sensitive cancer cells.
- View Dependent Claims (38, 41, 44, 73)
- 39. A method of inducing death of cancer cells, comprising contacting TRAIL-sensitive cancer cells with a polypeptide comprising amino acids 124 to 276 of SEQ ID NO:
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51. A method of killing cancer cells, contacting TRAIL-sensitive cancer cells with an oligomer comprising at least two TRAIL polypeptides, wherein each of said TRAIL polypeptides is a soluble fragment of the protein of SEQ ID NO:
- 2, wherein said oligomer kills TRAIL-sensitive cancer cells.
- View Dependent Claims (58, 63, 68, 76)
- 52. A method of inducing death of cancer cells, comprising contacting TRAIL-sensitive cancer cells with an oligomer comprising at least two TRAIL polypeptides, wherein each of said polypeptides comprises amino acids 124 to 276 of SEQ ID NO:
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79. A method of treating a mammal having cancer, comprising administering to the mammal a soluble, extracellular TRAIL polypeptide in an amount effective to induce cell death in the mammal'"'"'s cancer cells, wherein the TRAIL polypeptide comprises a soluble fragment of the TRAIL protein of SEQ ID NO:
- 2, wherein the N-terminal amino acid of said fragment is selected from residues 39 to 124 of SEQ ID NO;
2, and the C-terminal amino acid of said fragment is selected from residues 276 to 281 of SEQ ID NO;
2. - View Dependent Claims (80, 81, 82, 83)
- 2, wherein the N-terminal amino acid of said fragment is selected from residues 39 to 124 of SEQ ID NO;
- 84. A method of treating a mammal having cancer, comprising administering to the mammal a soluble, extracellular TRAIL polypeptide in an amount effective to induce cell death in the mammal'"'"'s cancer cells, wherein the TRAIL polypeptide comprises amino acids 124 to 281 of SEQ ID NO:
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86. A method comprising administering an oligomer to a human who has cancer, wherein said oligomer comprises at least two TRAIL polypeptides, wherein each of said polypeptides is a soluble fragment of the protein of SEQ ID NO:
- 2, wherein said oligomer kills TRAIL-sensitive cancer cells.
- View Dependent Claims (87, 88, 89, 90, 96)
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91. A method of killing target cells selected from the group consisting of cancer cells and virally-infected cells, comprising contacting the target cells with an oligomer comprising at least two TRAIL polypeptides, wherein each of said TRAIL polypeptides is a soluble fragment of the protein of SEQ ID NO:
- 2, wherein said oligomer kills TRAIL-sensitive target cells.
- View Dependent Claims (92, 93, 94, 95, 97)
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98. A method of inducing death of cancer cells in vitro, comprising contacting TRAIL-sensitive cancer cells with a soluble polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of:
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a) the extracellular domain of human TRAIL (amino acids 39 to 281 of SEQ ID NO;
2); and
b) a fragment of said extracellular domain;
wherein said polypeptide is capable of inducing apoptosis of Jurkat cells. - View Dependent Claims (99)
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100. A method of killing target cells in vitro wherein the target cells are cancer cells or virally-infected cells, comprising contacting the target cells with an oligomer comprising at least two TRAIL polypeptides, wherein each of said TRAIL polypeptides is a soluble fragment of the protein of SEQ ID NO:
- 2, wherein said oligomer kills TRAIL-sensitive target cells.
- View Dependent Claims (101)
Specification