Claims
- 1. A method for inducing apoptosis of a cell that comprises the α-chain of the granulocyte macrophage colony stimulating factor (GM-CSF) receptor, said method comprising the step of:contacting said cells with an effective amount of a modified GM-CSF polypeptide for a time and under conditions sufficient to induce apoptosis wherein said modified GM-CSF polypeptide comprises a mutation of the glutamate at position 21 of the amino acid sequence of wild-type native GM-CSF to an amino acid selected from the group consisting of: arginine, lysine, glutamine, and asparagine.
- 2. The method according to claim 1 wherein the modified GM-CSF binds to the α-chain of the GM-CSF receptor.
- 3. The method according to claim 1 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for glutamine in said modified GM-CSF.
- 4. The method according to claim 1 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for lysine in said modified GM-CSF.
- 5. The method according to claim 1 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for arginine in said modified GM-CSF.
- 6. The method according to claim 1 wherein the cells in which apoptosis is induced are normal or malignant myeloid cells.
- 7. The method according to claim 6 wherein the myeloid cells are myeloid leukemia cells.
- 8. The method according to claim 1 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for asparagine in said modified GM-CSF.
- 9. A method for treating myeloid leukemia cells in a human subject wherein said cells comprise the α-chain of the granulocyte macrophage colony stimulating factor (GM-CSF) receptor, said method comprising the step of:administering to said human subject an effective amount of a modified GM-CSF polypeptide for a time and under conditions sufficient to directly induce apoptosis wherein said modified GM-CSF polypeptide comprises a mutation of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF to an amino acid selected from the group consisting of: arginine, lysine, glutamine, and asparagine.
- 10. The method according to claim 9 wherein the modified GM-CSF binds to the α-chain of the GM-CSF receptor.
- 11. The method according to claim 9 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for glutamine in said modified GM-CSF.
- 12. The method according to claim 11 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for lysine in said modified GM-CSF.
- 13. The method according to claim 12 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for arginine in said modified GM-CSF.
- 14. The method according to claim 9 wherein the modified GM-CSF polypeptide comprises the substitution of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for asparagine in said modified GM-CSF.
- 15. The method according to claim 1 wherein the cells in which apoptosis is induced are normal or malignant myeloid cells.
- 16. The method according to claim 6 wherein the myeloid cells are myeloid leukemia cells.
- 17. A method for selecting bone marrow cells lacking the α-chain of the granulocyte macrophage colony stimulating factor (GM-CSF) receptor, said method comprising:(i) contacting said bone marrow cells with an effective amount of a modified GM-CSF polypeptide for a time and under conditions sufficient to induce apoptosis of cells expressing the α-chain of the GM-CSF receptor, wherein said modified GM-CSF polypeptide comprises a mutation of the glutamate at position 21 of the amino acid sequence of wild-type GM-CSF for arginine in said modified GM-CSF; and (ii) selecting cells that do not undergo apoptosis, said cells lacking said the α-chain of the GM-CSF receptor.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PN 3780 |
Jun 1995 |
AU |
|
Parent Case Info
This is a Continuation in Part of U.S. Pat. No. 5,939,063, issued Aug. 17, 1999, and is the U.S. National phase under 35 U.S.C §371 of International Application PCT AU96/00382, filed Jul. 28, 1999.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/AU96/00382 |
|
WO |
00 |
5/28/1998 |
5/28/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/00695 |
1/9/1997 |
WO |
A |
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5475087 |
Seelig et al. |
Dec 1995 |
|
5795966 |
Grabstein |
Aug 1998 |
|
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0409091A1 |
Jan 1991 |
EP |
0499161A2 |
Aug 1992 |
EP |
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Nov 1989 |
WO |
WO8911864 |
Dec 1989 |
WO |
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Jul 1991 |
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Non-Patent Literature Citations (4)
Entry |
Kinoshita, et al.; The EMBO Journa; vol. 14, No. 2, pp. 266-275; 1995; Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors. |
Han, et al.; Experimental Hematology 23: 265-272 (1995); Modulation of apoptosis in human myeloid leukemic cells by GM-CSF. |
Bach, et al.; Pathogenesis; Int Arch Allergy Immunol 1995; 107: 90-92; Evidence that Granuocyty/Macrophage-Colony-Stimulating Factor and Interferon-Maintain the Viability of Human Peripheral Blood Monocytes in Part by their Suppression of I1-10 Production. |
Iversen, et al.; Proc.Natl.Acad.Sci.USA; vol. 93, pp. 2785-2789; Apr. 1996; Apoptosis of hemopoietic cells by the human granulocyte-macrophage colony-stimulating factor mutant E21r. |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08/591438 |
Aug 1999 |
US |
Child |
08/983523 |
|
US |