Characterization and Immunotherapeutic Implications for a Novel Antibody Targeting Interleukin (IL)-13 Receptor α2

The high affinity interleukin-13 receptor alpha 2 (IL13R alpha 2) is selectively expressed at a high frequency by glioblastoma multiforme (GBM) as well as several other tumor types. One approach for targeting this tumor-specific receptor utilizes the cognate ligand, IL-13, conjugated to cytotoxic molecules. However, this approach lacks specificity because the lower affinity receptor for IL-13, IL13R alpha 1, is widely expressed by normal tissues. Here, we aimed to develop and characterize a novel monoclonal antibody (mAb) specific to IL13R alpha 2 for the therapeutic purpose of targeting IL13R alpha 2-expressing tumors. Hybridoma cell lines were generated and compared for binding affinities to recombinant human IL13R alpha 2 (rhIL13R alpha 2). Clone 47 demonstrated binding to the native conformation of IL13R alpha 2 and was therefore chosen for further studies. Clone 47 bound specifically and with high affinity (K-D = 1.39 x 10(-9) M) to rhIL13R alpha 2 but not to rhIL13R alpha 1 or murine IL13R alpha 2. Furthermore, clone 47 specifically recognized wild-type IL13R alpha 2 expressed on the surface of CHO and HEK cells as well as several glioma cell lines. Competitive binding assays revealed that clone 47 also significantly inhibited the interaction between human soluble IL-13 and IL13R alpha 2 receptor. Moreover, we found that N-linked glycosylation of IL13R alpha 2 contributes in part to the interaction of the antibody to IL13R alpha 2. In vivo, the IL13R alpha 2 mAb improved the survival of nude mice intracranially implanted with a human U251 glioma xenograft. Collectively, these data warrant further investigation of this novel IL13R alpha 2 mAb with an emphasis on translational implications for therapeutic use.