Monomeric CXCL12
The present invention provides a CXCL12 1 peptide engineered to resist peptide-induced dimerization by maintaining steric repulsion of the chemokine helix, pharmaceutical compositions thereof, and methods of using said dimer in the treatment of cancer, inflammatory disorders, autoimmune disease, and HIV/AIDS.
1. A constitutively monomeric CXCL12 peptide comprising the amino acid sequence of SEQ ID NO:1 wherein the amino acids at positions 55 and 58 are substituted with cysteine.
2. The CXCL12 peptide of claim 1 , wherein the peptide is CXCL12 1 having the amino acid sequence of SEQ ID NO:2.
3. A composition comprising the peptide of claim 1 , and a pharmaceutically acceptable carrier or diluent.
4. A method of treating cancer in a subject having cancer which expresses CXCR4 comprising administering to the subject having cancer a therapeutically effective amount of a composition comprising the CXCL12 peptide of claim 1 .
5. The method of claim 4 , wherein the cancer is selected from the group consisting of leukemia, lymphoma and myeloma.
6. A method of inducing apoptosis in cells expressing CXCR4 in a subject comprising administering to the subject a therapeutically effective amount of a composition comprising the CXCL12 peptide of claim 1 .
7. A method of treating leukemia in a subject having leukemia comprising administering to the subject a therapeutically effective amount of a composition comprising the CXCL12 peptide of claim 1 , wherein the leukemia comprises cells that express CXCR4.
8. The method of claim 7 , wherein the leukemia is myeloid leukemia.