Introduction of Imalumab

Imalumab (as known as Bax69) is a novel recombinant, fully-human, monoclonal antibody (mAb) which was designed and developed to target the macrophage migration inhibitory factor, with potential immunomodulating, anti-inflammatory and antineoplastic activities.

Mechanism of Action of Imalumab

MIF was originally discovered in 1966 as a lymphokine, derived from activated T-cells, that inhibited the random migration of macrophages in vitro and was shown to be involved in the mechanism of delayed-type hypersensitivity. Currently, it is known that MIF is a widely expressed and pleiotropic cytokine that functions as a critical upstream mediator of innate immunity and promotes numerous pathophysiological processes, such as glomerulonephritis, arthritis, experimental autoimmune encephalomyelitis (EAE), experimental autoimmune myocarditis (EAM), gram-negative and gram-positive sepsis, colitis, asthma diabetes, and pancreatitis. MIF is produced and secreted primarily by immune cells, such as lymphocytes, Mø, DC, neutrophils and pituitary cells. MIF secretion is tightly regulated by stress and immune stimuli, including endotoxins, inflammatory cytokines (interferon (IFN)-γ, tumor necrosis factor (TNF)-α) and glucocorticoids. Once secreted, MIF exhibits a broad range of immune and inflammatory activities, including the induction of inflammatory cytokines such as TNF-α, IFN-γ, interleukin (IL)-1β, IL-12, IL-6 and, CXCL8 (also known as IL-8), among others. In addition, MIF counter-regulates the immunosuppressive effects of glucocorticoids, and it sustains macrophage proinflammatory functions by inhibiting p53. Studies showing that MIF-specific blocking antibodies could attenuate endotoxic shock confirmed the critical role that MIF plays in innate immunity. MIF's unique biological activities have the potential to contribute to an in vivo microenvironment favoring tumor growth and invasiveness. These functional activities include: tumor suppressor downregulation, COX-2 and PGE2 upregulation, potent induction of angiogenesis and enhanced tumor growth, proliferation and invasiveness. At the same time, MIF directly promotes tumorigenesis by inhibiting p53 accumulation. Imalumab is a novel recombinant, fully human, monoclonal antibody targeting MIF with potential immunomodulating, anti-inflammatory and antineoplastic activities. Upon intravenous administration, imalumab binds to MIF, blocking its activity and preventing the MIF-mediated secretion of certain cytokines, including interleukin-1 beta and tumor necrosis factor-alpha. This may lead to an inhibition of cancer cell proliferation in MIF-overexpressing tumor cells. Preclinical data demonstrated imalumab has antitumor activity and acceptable toxicity.

Fig 1. Mechanism of Action of Imalumab

For research use only. Not intended for any clinical use.