Development of New Methods for Haematopoietic Precursors Mobilization

Yeda R&D Co. Ltd Israel flag

Israel

Abstract ID: 1545

The forced migration of hematopoietic stem/progenitor cells (HSPC) from the bone marrow (BM) into the peripheral blood (PB), termed mobilization, is important from a clinical point of view

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Introduction/Background

The forced migration of hematopoietic stem/progenitor cells (HSPC) from the bone marrow (BM) into the peripheral blood (PB), termed mobilization, is important from a clinical point of view as a procedure that allows for the collection of HSPC for transplantation in leukaemia patients. Granulocyte-colony stimulating factor (G-CSF), most frequently employed in the clinic, efficiently mobilizes HSPC after a few consecutive daily injections. Unfortunately, about 25 % of patients do not respond efficiently to currently recommended mobilization protocols and are termed poor mobilizers.

Aims/Hypothesis

The present invention provides a method of increasing mobilization of hematopoietic precursors from the bone marrow to the peripheral blood, by using either G-CSF with thrombin antagonists, or the antagonists alone.

Results

In the outlined technology it was found that enhancement of G-CSF levels is associated with enhancement of stem cell mobilization from the bone marrow to the spleen. Likewise, inhibitors of the interaction between thrombin and its receptors (known as PAR) could enhance the effect of G-CSF. Therefore, PAR antagonists are synergistic with G-CSF, leading to marked enhancement of stem cell mobilization. Considering that G-CSF is controversial due to several side effects, this invention might enable using lower doses of G-CSF or replace it altogether by thrombin antagonists. The currently lengthy procedure may be shortened using this invention.

Conclusion

We have developed a method for increasing the mobilization of hematopoietic stem cells.

Relevance/Opportunity

Treatment of cancer, by upregulation of a factor of the coagulation cascade and inhibition of mobilization (since solid tumours depend on bone marrow-derived cells for tumour vascularisation and survival). Please enquire quoting reference no. 1545 regarding licensing or codevelopment partnerships.

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Last Updated May 2015