Interleukin-1 receptor type 2 (IL1R2) is a decoy receptor that binds pro-inflammatory cytokines IL-1α and IL-1β, modulating the IL-1 signaling pathway. Unlike the signaling receptor IL1R1. IL1R2 lacks an intracellular Toll/IL-1 receptor (TIR) domain, enabling it to competitively inhibit IL-1-mediated inflammation without activating downstream pathways. This regulatory mechanism makes IL1R2 a potential therapeutic target in inflammatory diseases, autoimmune disorders, and cancers where IL-1 signaling is dysregulated.
Antibodies targeting IL1R2 are designed to either block its function or exploit its overexpression in certain tissues. For instance, neutralizing antibodies can prevent IL1R2 from sequestering IL-1 cytokines, thereby restoring balanced immune responses. Conversely, agonist antibodies may enhance IL1R2’s natural anti-inflammatory role in hyperinflammatory conditions. In oncology, IL1R2 is overexpressed in some tumors, and antibody-drug conjugates (ADCs) or bispecific antibodies targeting IL1R2 are being explored for tumor-selective therapy.
Recent studies highlight IL1R2 antibodies in preclinical/clinical development for rheumatoid arthritis, sepsis, and solid tumors. Challenges include ensuring specificity to avoid off-target effects on IL1R1 and optimizing pharmacokinetics for tissue penetration. Overall, IL1R2 antibodies represent a versatile toolset for fine-tuning IL-1-driven pathologies, with ongoing research focused on expanding their therapeutic applications.