Treating multiple myeloma with inhibitors of CXCR4
Inventors: Ulrich Von Andrian, Irina Mazo, Jean-Marc Gauguet
Invention Types: Therapeutics
Research Areas: Oncology/Hematology, Stem Cell
Keywords: Method of Use, Small Molecule/DrugFor More Information Contact: Dietz, Ryan
Researchers at the Immune Disease Institute have found that treating multiple myeloma may be possible with inhibitors of CXCR4, such as AMD3100 and anti-CXCR4 antibodies. The CXCR4 inhibitor disrupts or impedes the CXCR4 binding to the chemokine SDF-1a/CXCL12. The inhibitor is administered to the subject in need of such treatment as a pharmaceutical composition in amounts effective to interrupt the CXCR4-SDF pathway and to treat this disease. In experiments, a decreased expression of CXCR4 on multiple myeloma cells resulted in decreased homing of the cells to the bone marrow and a reduction in the development of the disease.
SDF-1a/CXCR4 signaling is active in the majority of cancer cells, including chronic lymphoid leukemia (CLL), chronic myeloid leukemia (CML), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL). In addition, this signaling pathway is also active in solid tumors, such as rhabdomyosarcoma, prostate cancer and melanoma. Breast and lung cancers are known to metastasize to the bone marrow, using the SDF-1a/CXCR4 pathway in the process.
• These treatment methods can be used independently, or in conjunction with, other therapies for the treatment of multiple myeloma.
• This treatment may also be used for chronic lymphoid leukemia (CLL), chronic myeloid leukemia (CML), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL).
• The pharmaceutical composition is administered to a human subject over an extended period of time, for at least about 24 hours, and preferably at least about 6 days, and more preferably form about 6 days to about 40 days. The pharmaceutical composition typically includes a physiologically acceptable carrier and an adjuvant.
• The pharmaceutical composition can be used independently of other therapeutic compositions, or in combination with such other therapeutics.
• The pharmaceutical composition negatively affects homing and survival of multiple myeloma cells, originated somewhere else, in the bone marrow, the major targeted organ. Thus, the treatment targets the primary mechanism of multiple myeloma development.
Outlicensing and research collaboration
Key Publications: US Patent 7,825,088; Published US 2011/0070244 A1