New peptides for improving the recruitment of stem cells for transplantation.
Blood cancers (leukemia, lymphoma and myeloma) are very common: they accounted for nearly 9.5 percent of deaths in the US from cancer in 2009. Stem cell transplantation, which aims to restore the function of the marrow, is an important therapy for these malignancies. Successful blood and marrow transplant requires the infusion of a sufficient number of hematopoietic stem and progenitor cells (HSPC), which is done by recruitment of HSPC from the marrow into the blood (mobilization). Currently used clinical procedures to produce stem cell mobilization include administration of G-CSF or GM-CSF, either as single agents or in combination with chemotherapy. However, some autologous blood stem cell donors exhibit indifference to currently applied mobilization therapies. Hence, improved methods to mobilize peripheral blood HSPC are warranted. The present invention is directed to novel short peptides of beta-defensins for improving the mobilization of HSPC.
· Non-toxic, derived from a physiological molecule of innate host immunity
· Cheap and simple synthesis
· Rapid, robust and preferential mobilization of immature HSPC
· Enhancement of mobilizing efficiency of presently used substances (e.g. G-CSF)
· Dual use of the derivatives
Beta-defensins belong to a family of antimicrobial peptides, a major component of the innate immune system. In a mouse model, two different linear beta-defensin-derived peptides provided a strong and rapid HSPC mobilization, alone and in combination with G-CSF, a cytokine that is the major agent inducing robust mobilization of HSPC. In addition, a cyclic peptide derivative effectively inhibited HSPC mobilization and proliferation, as well as human malignant cell motility in mice. These findings make beta-defensin-derived peptides as promising small molecule candidates for improving current clinical HSPC mobilization protocols, and their cyclic derivatives as promising candidates for reducing cancer cell development and metastasis in patients.