Abstract
Macrophage Migration Inhibitory Factor (MIF) is a multifunctional cytokine, that upon binding to its main receptor, CD74, promotes angiogenesis, cell survival, and the expression of pro-inflammatory cytokines. This cytokine has been recognized as a biomarker of different autoimmune and cardiovascular diseases, metabolic disorders, systemic infections, and several types of cancer. The blockade of MIF by small synthetic compounds (ISO-1; ISO-66), or its genetic ablation in several cancer models resulted in a significant tumor reduction, confirming its pro-tumoral role. In this regard, our laboratory has identified anti-mouse/human MIF cross-reactive nanobodies (Nbs, i.e. recombinant variable domains of heavy-chain-only antibodies), that were able to prevent endotoxic shock in an experimental murine model. In addition, when used as a monotherapy, these anti-MIF Nbs significantly reduced the MC-38 colorectal cancer tumor growth by promoting an anti-tumoral immune response. Additionally, when combined with anti-PD-1 treatment, a superior tumor regression was observed compared to the use of anti-PD-1 monotherapy alone.
Finally, the tailorability of the Nbs could also facilitate the design of multivalent Nb constructs directed against MIF.
Finally, the tailorability of the Nbs could also facilitate the design of multivalent Nb constructs directed against MIF.
Original language | English |
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Publication status | Published - 19 Sep 2023 |
Event | The Single-Domain Antibodies 2023 meeting: 3rd congress on single-domain antibodies - CIS auditorium, Institut Pasteur, Paris, France Duration: 18 Sep 2023 → 20 Sep 2023 https://www.nanobodies2023.conferences-pasteur.org |
Conference
Conference | The Single-Domain Antibodies 2023 meeting |
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Country/Territory | France |
City | Paris |
Period | 18/09/23 → 20/09/23 |
Internet address |