The use of the Nanobody Technology to Block the MIF-CD74 Interaction.

Amanda Sparkes, Benoit Stijlemans, Steve Schoonooghe, Gholamreza Hassanzadeh Ghassabeh, Lin Leng, Richard Bucala, P. De Baetselier

Onderzoeksoutput: Meeting abstract (Book)

Samenvatting

Cytokines play a critical role in the immune system as they are responsible for initiating and coordinating
the host inflammatory responses. Although essential for the control of an invader, deregulation of such
cytokines can culminate into major problems for the host, leading to a wide variety of chronic inflammatory
diseases. The involvement of the interaction between macrophage migration inhibitory factor (MIF) and its
receptor (CD74) has been identified as a key culprit in prolonging the inflammatory status/disease
pathology in a variety of disease processes including autoimmune diseases, metabolic disorders, systemic
infections as well as sepsis and cancer. The upstream actions in the inflammatory cascade and the ability
to sustain inflammatory responses make targeting the MIF/CD74 axis an attractive, steroid sparing,
therapeutic strategy. However, recently a MIF homologue (i.e. D-DT) has been identified rendering current
MIF-targeting strategies insufficient. CD74 is found primarily on antigen presenting cells, has a high
turnover rate and its expression is up-regulated during infection, making it a prime target. Therefore, we
developed single domain antigen-binding fragments of camelid heavy-chain antibodies (termed
Nanobodies; Nbs) to specifically target CD74, thereby blocking both the MIF and D-DT mediated effects.
Hereby, we demonstrated that the anti-CD74 Nbs could (i) specifically recognize CD11b+Ly6c+ monocytic
cells, (ii) block binding of MIF/D-DT on intact cells and (iii) block MIF-mediated TNF induction following
LPS stimulation of myeloid cells. Therefore, we hypothesize that the Nb-based targeting of CD74 may
offer a novel and more efficient therapeutic strategy to block MIF/CD74-mediated pathological effects.
Originele taal-2English
TitelEMDS Erlangen
StatusPublished - 10 dec 2013
EvenementUnknown - Erlangen, Germany
Duur: 10 okt 201312 okt 2013

Conference

ConferenceUnknown
Land/RegioGermany
StadErlangen
Periode10/10/1312/10/13

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