Researchers from the Division Medicinal Chemistry (led by Prof. Martine Smit and Prof. Rob Leurs) and the Belgian Biotech company Ablynx have discovered the first llama-derived single chain antibody (nanobody) targeting the CXCR4 chemokine receptor, a protein that plays a key regulatory role in hematopoietic stem cell trafficking.

Ablynx has developed and initiated a Phase I clinical trial in healthy volunteers with the therapeutic nanobody ALX-0651, for use in stem cell mobilisation. ALX-0651 is the first Nanobody in clinical trials targeting a GPCR, a target class that has proven to be difficult to address with conventional antibodies.

Blocking CXCR4 effectively releases the hematopoietic stem cells from the bone marrow and allows them to be mobilised to the peripheral blood for collection and subsequent transplantation in patients.Hematopoietic stem cell transplantation is used to reconstitute the bone marrow and repopulate the blood and immune system in patients whose immune system has been depleted of stem cells as a result of high-dose chemotherapy. It has become a widely used procedure in patients with multiple myeloma and non-Hodgkin's lymphoma.

The Phase I study will evaluate the safety and tolerability of ALX-0651. The study will investigate the PK/PD and immunogenicity profile of the Nanobody and will establish one or more biologically effective dose levels and/or the maximum tolerated dose.

• Jähnichen et al. (2010) PNAS 107: 20565