IL-13Rα2

Interleukin-13 receptor alpha 2 (IL-13Rα2, CD213a2) is a high-affinity IL-13 binding protein that differs fundamentally from its sibling IL-13Rα1. It binds IL-13 with approximately 50-fold higher affinity, exists partly as a soluble decoy, and possesses an extremely short 17-amino-acid cytoplasmic tail lacking box 1 and STAT docking motifs, so it was long considered a pure decoy receptor. IL-13Rα2 is barely detectable in normal tissues but is strongly upregulated in glioblastoma, colorectal, ovarian, pancreatic and breast cancers, where it correlates with invasion, metastasis and poor prognosis. Newer work shows membrane IL-13Rα2 can signal in a TMEM219/ERK/AP-1-dependent manner promoting TGF-β production and fibrosis in asthma and liver disease. This restricted, tumor-selective expression has made IL-13Rα2 a premier target for tumor-specific delivery: IL-13 PE38 immunotoxins, bispecific antibodies and IL-13Rα2-directed CAR-T cells have reached clinical trials for glioblastoma.