MIF – macrophage migration inhibitory factor
Macrophage migration inhibitory factor (MIF) is a pleiotropic chemokine consisting of three identical subunits, that is driving tumorigenic cell signaling and exerting immunomodulatory activities in the tumor microenvironment (Mitchell et al., 2002). In patients, MIF has been associated with high tumor burden, increased metastasis risk, and poor prognosis (Krockenberger et al., 2012).
MIF is also a pro-inflammatory cytokine and counter-regulator of exogenous and endogenous glucocorticoids (Calandra and Roger, 2003). It is implicated in acute and chronic inflammatory conditions, such as inflammatory bowel disease, systemic lupus erythematosus or rheumatoid arthritis.
MIF is markedly different from other cytokines and chemokines because it is constitutively expressed, stored in the cytoplasm and is present in the circulation of healthy subjects (Roger et al., 2017). Due to its ubiquitous nature, MIF may be considered as an inappropriate target for therapeutic intervention.
oxMIF – oxidized macrophage migration inhibitory factor
The founders of OncoOne discovered a disease-related isoform of MIF, designated oxMIF (oxidized MIF) (Thiele et al., 2015). OxMIF is generated by a posttranslational modification of MIF in inflammatory processes and tumorigenesis. Unlike MIF, oxMIF is differentially expressed in healthy and diseased tissue and can be detected in inflamed tissues and solid tumors (Thiele et al., 2015; Schinagl et al., 2016). Importantly, the post-translational modification leads to a structural transformation that exposes epitopes in the MIF trimer that are otherwise inaccessible to antibodies in the center of the trimer. Targeting oxMIF as the disease related isoform of MIF, overcomes the challenges of targeting MIF and makes oxMIF ideal for therapeutic intervention.