IL1RAP (Interleukin 1 Receptor Accessory Protein) is a transmembrane co-receptor essential for signaling pathways mediated by interleukin-1 (IL-1), IL-33. and IL-36 cytokines. As a member of the IL-1 receptor family, IL1RAP partners with primary receptors like IL-1R1 or IL-33R to form functional signaling complexes. Upon ligand binding, it recruits adaptor proteins (e.g., MYD88) to activate downstream NF-κB and MAPK pathways, driving inflammatory and immune responses.
IL1RAP is broadly expressed on immune cells (e.g., macrophages, dendritic cells) and certain cancer cells, including myeloid malignancies and solid tumors. Its overexpression in diseases like chronic inflammation, autoimmune disorders, and cancers has made it a therapeutic target. IL1RAP-targeting antibodies are designed to block pro-inflammatory signaling or induce antibody-dependent cellular cytotoxicity (ADCC) against malignant cells. For example, in oncology, anti-IL1RAP antibodies have shown potential in depleting leukemia stem cells in acute myeloid leukemia (AML) or sensitizing tumors to immunotherapy.
Recent clinical trials explore IL1RAP antibodies (e.g., Nidanilimab, CAN04) for cancers and inflammatory conditions, leveraging its dual role in modulating immune activation and tumor microenvironment. Research continues to optimize specificity and therapeutic efficacy while minimizing off-target effects.