Blocking of MIF by generating anti-CD74 nanobodies.

Student thesis: Master's Thesis

Abstract

Many inflammation-associated diseases occur commonly in developed countries. The treatment of these diseases is usually non-curative and is aimed at suppressing inflammatory end-organ damage. The involvement of macrophage migration inhibitory factor (MIF) and its receptor (CD74) in inflammation-associated pathologies has been intensively studied by many research groups. Hereby, this interaction has been identified as a key culprit in prolonging inflammatory status in a wide variety of disease processes including autoimmune diseases, metabolic disorders, systemic infections as well as sepsis and cancer. The upstream actions in the inflammatory cascade make MIF an attractive therapeutic target in different acute and chronic inflammatory diseases as well as in cancer. As such, it is critical to consider that specific MIF antagonists may offer new therapeutic avenues for MIF associated pathologies. Much effort has gone into directly blocking MIF via antibodies or synthetic molecules however alternative means of generating MIF antagonists could offer additional, perhaps even better, therapeutic alternatives. Herein, we demonstrate the use of Nanobody technology to directly target the receptor for MIF, CD74. As such, one Nanobody has been obtained against recombinant human CD74 73-232 which binds with nanomolar affinity. We demonstrate the ability of this Nanobody to inhibit the binding of MIF to CD74 and its subsequent antagonistic properties. Furthermore we validate the role of the MIF/CD74 axis in the development of anemia of chronic disease using African trypanosomiasis as a model.
Date of Award4 Sep 2012
Original languageEnglish
SupervisorPatrick De Baetselier (Promotor) & Benoit Stijlemans (Advisor)

Keywords

  • MIF
  • CD74
  • Nanobodies
  • African Trypanosomiasis

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