Bcr-Abl directed compositions and uses for inhibiting Philadelphia chromosome stimulated cell growth
US6107457A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Feb 16, 1995 |
| Grant date | Aug 22, 2000 |
| Priority date | — |
| Expiry date | Feb 16, 2015 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K38/00
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
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 …
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