Mathijs Broeren
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Email: mathijs.broeren[at]ru.nl Phone: +31(0)24 3610559 HG: lab 03.318 |
Characterization of therapeutic anti-CXCR4 antibodies
C-X-C chemokine receptor 4 (CXCR4) is a G protein-coupled receptor, expressed by different (hematological) cancer cells and immune cells. Activation of CXCR4 by its ligand C-X-C motif ligand 12 (CXCL12) activates different oncological signaling pathways in cancer cells and can stimulate immune cells. Moreover, cancer cells can migrate to CXCL12-expressing tissues, where they are less susceptible to treatment. Blocking CXCR4 can inhibit cancer cell signaling and make them more sensitive to therapy. In addition, dysregulation of the CXCR4 network has been reported to be associated with autoimmune conditions.
In this project, I characterize therapeutic antibodies against CXCR4, which have been selected from large scFv phage libraries and engineered into complete human(ized) antibodies in collaboration with ModiQuest BV. I will determine their affinity, specificity and to what extent they can block CXCR4 activation in vitro. The most efficiently interfering antibodies will be humanized to make them suitable for future applications. These antibodies will be expressed and tested in advanced (co)-culture systems to explore if the antibodies can inhibit CXCL12-induced migration and CXCL12-induced cell activation. The purpose of the project is to generate potent therapeutic anti-CXCR4 antibodies that in the long run may be applicable for treatment of both cancer patients and autoimmune patients.