Abstract
G protein‐coupled receptors (GPCRs) represent a major therapeutic target class as they play a key role in cellular communication. GPCRs have been successfully targeted with small molecules. With new and improved immunization‐related technologies and advances in GPCR purification and expression techniques, antibody‐based targeting of GPCRs has gained attention. Nanobodies, llama‐derived antibodies, are a relatively novel class of antibodies, which combine the advantages of both small molecules (e.g., molecular cavity binding, ease of production) and monoclonal antibodies (e.g. high affinity and specificity). We have identified the first inhibitory nanobodies targeting chemokine receptors, which play a role in leukocyte trafficking and are implicated in several pathologies, such as inflammatory diseases, cancer and HIV. We have identified nanobodies targeting the chemokine receptors CXCR4 and CXCR7. These nanobodies appeared to effectively modulate CXCR4 (stem cell mobilization, HIV co‐receptor activity) and CXCR7 (tumor progression) function in vitro and/or in vivo. In addition, we identified nanobodies targeting chemokines, acting as neutralizing antibodies. Hence nanobodies targeting the chemokine receptor system serve as interesting research tools, diagnostics and potentially therapeutics which may contribute to advancements in chemokine receptor research.
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