Cancer

Patient sample and mouse studies suggest inhibiting IL-18 or NLRP1 could help treat MM. In patient samples, high bone marrow plasma levels of IL-18 correlated with poor overall survival. In two mouse models of MM, systemic knockout of IL-18 or NLRP1 increased survival and decreased numbers of malignant plasma cells in the bone marrow compared with normal IL-18 or NLRP1 expression. In both MM models, an IL-18 neutralizing mAb plus Velcade bortezomib increased survival compared with either agent alone. In one of the models, the anti-IL-18 mAb increased survival compared with a control IgG. Ongoing work includes testing the IL-18 mAb in combination with undisclosed therapies in additional models of MM.

Takeda Pharmaceutical Co. Ltd. and Johnson & Johnson market Velcade, a small molecule dipeptide boronic acid proteasome inhibitor, to treat MM and mantle cell lymphoma (MCL) and have the compound in Phase III testing to treat B cell lymphoma...