Characterization and immunotherapeutic implications for a novel antibody targeting interleukin (IL)-13 receptor α2.
The high affinity interleukin-13 receptor α2 (IL13Rα2) 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, IL13Rα1, is widely expressed by normal tissues. Here, we aimed to develop and characterize a novel monoclonal antibody (mAb) specific to IL13Rα2 for the therapeutic purpose of targeting IL13Rα2-expressing tumors. Hybridoma cell lines were generated and compared for binding affinities to recombinant human IL13Rα2 (rhIL13Rα2). Clone 47 demonstrated binding to the native conformation of IL13Rα2 and was therefore chosen for further studies. Clone 47 bound specifically and with high affinity (K(D) = 1.39 × 10(-9) M) to rhIL13Rα2 but not to rhIL13Rα1 or murine IL13Rα2. Furthermore, clone 47 specifically recognized wild-type IL13Rα2 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 IL13Rα2 receptor. Moreover, we found that N-linked glycosylation of IL13Rα2 contributes in part to the interaction of the antibody to IL13Rα2. In vivo, the IL13Rα2 mAb improved the survival of nude mice intracranially implanted with a human U251 glioma xenograft. Collectively, these data warrant further investigation of this novel IL13Rα2 mAb with an emphasis on translational implications for therapeutic use.
The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA. ibalyasn@surgery.bsd.uchicago.edu
Irina V
IV
Balyasnikova
Derek A
DA
Wainwright
Elena
E
Solomaha
Gina
G
Lee
Yu
Y
Han
Bart
B
Thaci
Maciej S
MS
Lesniak
D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000494:pharmacology; D000915:Antibody Affinity / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D006825:Hybridomas; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D053663:Interleukin-13 Receptor alpha2 Subunit