AVTX-007 is a fully human anti-interleukin (IL)-18 monoclonal antibody with the potential to address multiple immune-mediated diseases, including Still’s disease and certain cancers like relapsed or refractory multiple myeloma.
IL-18 is a proinflammatory cytokine with pleiotropic and immunoregulatory effects. IL-18 is characterized by its ability to induce production of interferon-gamma (IFN-g) and other inflammatory cytokines from natural killer (NK) and T helper 1 (Th1) cells in synergy with IL-12. It has been shown to play a critical role in various autoinflammatory diseases, such as Still’s disease, as well as in the inflammation and immunosuppression associated with multiple myeloma.
Still’s disease is a rare systemic inflammatory disorder of unknown cause. Affected individuals may develop episodes of high, spiking fevers, a pink or salmon colored rash, joint pain, muscle pain, sore throat, and other symptoms associated with systemic inflammatory disease.
Elevated levels of IL-18 have been shown to be correlated with disease activity in patients with active Still’s disease.
Serum IL-18 Significantly Elevated in AOSD
Multiple myeloma is a cancer that forms in plasma cells. Cancerous plasma cells accumulate in the bone marrow, compromising the body's ability to produce antibodies that fight infection. IL-18 is essential for liquid tumor growth, survival, and metastasis, as well as local immunosuppression. Targeting IL-18 can increase tumor immune cell access by inhibiting tumor-induced immune suppression.
IL-18 and the Tumor Microenvironment
Elevated levels of IL-18 have been shown to be correlated with significantly worse median survival (42 mo vs >84 mo; P=0.0026; HR, 1.84) in patients with multiple myeloma. Reducing IL-18 levels has been shown to prolong survival in rodent models.
Elevated IL-18 Correlated With Poor Survival