Definition

A human immunoglobulin G1 (IgG1) monoclonal antibody against the p28 subunit of the immunosuppressive cytokine interleukin-27 (IL-27p28), with potential immune-activating, pro-inflammatory and antineoplastic activities. Upon administration, casdozokitug targets and binds to IL-27p28, and inhibits the interaction of IL-27 with the IL-27 receptor subunit alpha (IL-27RA). This prevents the activation of IL-27RA and prevents IL-27-mediated signaling. This reduces signal transducer and activator of transcription 1 (STAT1) phosphorylation which leads to increased secretion of pro-inflammatory cytokines, such as interferon-gamma (IFN-g) and tumor necrosis factor-alpha (TNF-a). It also decreases the expression of inhibitory immune checkpoint receptors, such as programmed death-ligand 1 (PD-L1), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and lymphocyte-activation gene 3 (LAG3), on immune cells. This may enhance a T-cell mediated immune response against tumor cells that rely on IL-27 for immune escape. IL-27, a heterodimeric member of the IL-12/IL-23 cytokine family composed of IL-27p28 and Epstein-Barr virus induced gene 3 (EBI3), plays an important role in the immunosuppressive tumor microenvironment (TME). IL-27 signals through the JAK-STAT pathway to limit the duration and intensity of a T cell-mediated immune response during infection and cancer by altering immunoregulatory receptor expression and proinflammatory cytokine secretion.