Anti-Human IFNy (Emapalumab)

IFNγ plays roles in Th1 differentiation, macrophage function, leukocyte migration to sites of infection, and increasing major histocompatibility complex expression to improve T-cell recognition of infected or malignant cells 1.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe dysregulation of the immune system characterized by increased IFNγ production, macrophage and lymphocyte hyperactivity with tissue infiltration, hypersecretion of pro-inflammatory cytokines (CXCL9), hemophagocytosis, tissue damage, and multi-organ failure 2.

IFNγ plays a central role in the pathophysiology of HLH, and blocking IFNγ leads to clinical improvement. Emapalumab was developed by Novimmune and Swedish Orphan Biovitrum as an immunotherapeutic treatment for HLH 2.

Emapalumab is a fully human IgG1 monoclonal antibody that targets and binds to IFNγ with high affinity.

Emapalumab neutralizes IFNγ activity and inhibits interaction with its receptor by acting as a non-competitive inhibitor binding to free IFNγ and IFNγ-Receptor-1(IFNγR1)-bound IFNγ.

Emapalumab inhibits receptor dimerization and transduction of interferon-γ signaling, impairing the interaction induced by IFNγ at the cell surface with IFNγR1 and IFNγ R2 and thereby neutralizing IFNγ biologic activity 2,3,4.

Emapalumab prevents recruitment of IFNγR2 but has no effect on IFNγR1 endocytosis and internalization into lysosomes 2,4.

In HLH patients, emapalumab reduces the plasma concentrations of the cytokine CXCL9. Emapalumab is composed of anti-(human IFNγ) human monoclonal NI-0501 heavy chain, disulfide with human monoclonal NI-0501 light chain, dimer 2.

Emapalumab is produced by recombinant DNA technology and is approximately 148 kDa 5.