Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues
Patent
1995-02-16
2000-08-22
Brusca, John S.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
530324, 530326, 530327, 530328, 530329, 530330, C07K 700, C07K 1400
Patent
active
061074578
ABSTRACT:
Compositions comprising a mixture of peptides that bind to molecules involved in Bcr-Abl oncoprotein function are disclosed. In addition, expression of functional BCR protein (p160 BCR) or amino terminal fragments thereof (159, 221 and 413 amino terminal residues) by way of retrovirus vectors will oppose the biological function of Bcr-Abl (p160 BCR) or inactivate Bcr-Abl tyrosine kinase function or its signal transduction function. Bcr and Abl peptides, either tyrosine phosphorylated or unphosphorylated, that bind to a region near the amino terminus of Bcr to prevent formation of tetramer Bcr-Abl molecules, that bind to the SH2 domain of Grb2, to sites on tyrosine phosphorylated Shc protein, to sites of Crkl, and to an SH2 domain of Ras Gap comprise particular peptide preparations of the invention. The peptides and polypeptides inhibit Bcr-Abl oncoprotein activation, or block the oncogenic signal generated by the Bcr-Abl oncoprotein and, thereby, inhibit growth and induce cell death of leukemia cells expressing the oncoprotein. Methods for processing bone marrow using the peptide and polypeptide compositions of the invention are also provided. Stem cells present in bone marrow may thus be enriched for Philadelphia chromosome-negative cells prior to transplantation, particularly as part of autologous bone marrow transplant therapy of leukemia, including CML, ALL and AML.
REFERENCES:
patent: 4599305 (1986-07-01), Witte et al.
patent: 5334761 (1994-08-01), Gebeyehu et al.
patent: 5763571 (1998-06-01), Avruch et al.
patent: 5795859 (1998-08-01), Rathjen et al.
Lu et al., "Tyrosine Phosphorylation of P160 BCR by P210 BCR-ABL", Blood, 82(4):1257-1263, 1993.
Maxwell et al., "Analysis of P210.sup.bcr-abl Tyrosine Protein Kinase Activity in Various Subtypes of Philadelphia Chromosome-positive Cells from Chronic Myelogenous Leukemia Patients", Cancer Research, 47:1731-1739, 1987.
Druker et al., "Tyrosine Phosphorylatino of rasGAP and Associated Proteins in Chronic Myelogenous Leukemia Cell Lines," Blood, 79(9):2215-2220, 1992.
Hou et al., "An Interleukin-4-Induced Transcription Factor: IL-4 Stat," Science, 265:1701-1706, 1994.
Liu et al., "BCR-ABL tyrosine kinase is autophosphorylated or transphosphorylates P160 BCR on tyrosine predominantly within the first BCR exon," Oncogene, 8:101-109, 1993.
McWhirter et al., "A Coiled-Coil Oligomerization Domain of Bcr is Essential for the Transforming Function of Bcr-Abl Oncoproteins," Molecular and Cellular Biology, 13(12):7587-7595, 1993.
McWhirter and Wang, "An actin-binding function contributes to transformation by the Bcr-Abl oncoprotein of Philadelphia chromosome-positive human leukemias," The EMBO Journal, 12(4):1533-1546, 1993.
Okabe et al., "Effect of Herbimycin A, an Antagonist of Tyrosine Kinase, on bcr/abl Oncoprotein-Associated Cell Proliferations: Abrogative Effect on the Transformation of Murine Hematopoietic Cells by Transfectin of a Retroviral Vector Expressing Oncoprotein P210.sup.bcr/abl and Preferential Inhibition on Ph.sup.1 -Positive Leukemia Cell Growth," Blood, 80(5):1330-1338, 1992.
Pawson and Gish, "SH2 and SH3 Domains; From Structure to Function," Cell, 71:359-362, 1992.
Pendergast et al., "BCR-ABL-Induced Oncogenesis Is Mediated by Direct Interaction with the SH2 Domain of the GRB-2 Adaptor Protein," Cell, 75:175-185, 1993.
Puil et al., "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway," The EMBO Journal, 13(4):764-773, 1994.
Tauchi et al., "Coupling between p210bcr-abl and Shc and Grb2 Adaptor Proteins in Hematopoietic Cells Permits Growth Factor Receptor-indpendent Link to Ras Activation Pathway," J. Exp. Med., 179:16-175, 1994.
Tauchi et al., "SH2-containing Phosphotyrosine Phosphatase Syp Is a Target of p210bcr-able Tyrosine Kinase," The Journal of Biological Chemistry, 269(21):15381-15387, 1994.
Hoeve et al., "Tyrosine Phosphorylation of CRKL in Ph-Positive Leukemia," Blood, 84(6):1731-1736, 1994.
Hoeve et al., "Cellular Interactions of CRKL, and SH2-SH3 Adaptor Protein," Cancer Research, 4:2563-2567, 1994.
Arlinghaus Ralph B.
Liu Jiaxin
Lopez-Berestein Gabriel
Lu Dai
Board of Regents , The University of Texas System
Brusca John S.
McGarry Sean
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