IL13RA2 (Interleukin-13 Receptor Subunit Alpha 2) is a cell surface protein that binds interleukin-13 (IL-13) with high affinity, though it lacks canonical signaling domains. Unlike the functional IL13RA1/IL4RA heterodimer, IL13RA2 is considered a decoy receptor that modulates IL-13 activity, potentially dampening its pro-inflammatory and pro-fibrotic effects. However, IL13RA2 is overexpressed in various cancers, including glioblastoma, colorectal carcinoma, and ovarian cancer, where it may promote tumor invasiveness, angiogenesis, and immune evasion. This tumor-specific overexpression makes IL13RA2 a compelling therapeutic target.
Antibodies targeting IL13RA2 are designed to block its oncogenic interactions or deliver cytotoxic payloads directly to cancer cells. For example, immunotherapies like CAR-T cells or antibody-drug conjugates (ADCs) leveraging IL13RA2 antibodies have shown promise in preclinical and early clinical trials. Notably, IL13RA2-targeted CAR-T therapies have been explored for glioblastoma, demonstrating feasibility in phase I studies. Challenges include tumor heterogeneity in IL13RA2 expression and potential off-target effects, though its limited presence in healthy tissues may reduce toxicity risks.
Research continues to optimize antibody specificity, affinity, and delivery mechanisms to enhance therapeutic efficacy. These efforts highlight IL13RA2’s dual role as a regulatory receptor and a cancer biomarker, positioning it at the intersection of immunology and oncology.