Anti-Human IL-1RAP (IL-1R3) (Nadunolimab) – Fc Muted™ (I-2145-500ug)

IL-1RAP (interleukin-1 receptor accessory protein) is a co-receptor that works with the IL-36 subfamily of the IL-1 interleukin family1. Members of the IL-1 family play key signaling roles in innate and adaptive immunity. IL-1RAP is particularly involved in promoting inflammatory responses via the IL-1, IL-33, and IL-36 signaling pathways. IL-1RAP also plays a role in cancer promotion, progression, and metastasis. Additionally, IL-1RAP dimerizes with IL-1R1 to initiate signaling of IL-1α and IL-1β, both of which promote chemotherapy resistance2. As such, IL-1RAP is a target for cancer therapy1. Two different therapies targeting IL-1RAP are under development: 1) chimeric antigen receptor T-cells (CAR-T) therapy and 2) antibody immunotherapy for either direct blockade or activation of antibody-dependent cell-mediated cytotoxicity (ADCC). Nadunolimab was generated by grafting the complementarity-determining regions of a murine monoclonal antibody into a human IgG1 isotype3. BALB/c mice were immunized with a fusion protein of the extracellular part of IL-1RAP (Pro100-Lys330) and the Fc-part of human IgG1. Splenocytes were fused with mouse myeloma cell line Sp2/0 and screened by ELISA for binding to the IL-1RAP extracellular domain3,4. Nadunolimab binds IL-1RAP in a manner that blocks IL-1α and IL-1β as well as partially inhibits IL-33 signaling. Nadunolimab binds to the top of the IL-1RAP D2 domain, specifically to residues 105-114, 145-158, and 169-1765. Residues Thr154 to Ile171 are necessary for binding, with Q165 being critical. Additionally, binding is directly coincident with portions of the IL-1β and IL-33 signaling complexes. Alternative names for nadunolimab are CAN04 and mAb3F8.