Characterization and immunotherapeutic implications for a novel antibody targeting interleukin (IL)-13 Receptor α2

Irina V. Balyasnikova*, Derek A. Wainwright, Elena Solomaha, Gina Lee, Yu Han, Bart Thaci, Maciej S. Lesniak

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 (KD = 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.

Original languageEnglish (US)
Pages (from-to)30215-30227
Number of pages13
JournalJournal of Biological Chemistry
Volume287
Issue number36
DOIs
StatePublished - Aug 31 2012

Fingerprint

Interleukin-13 Receptors
Antibodies
Clone Cells
Tumors
Interleukin-13
Monoclonal Antibodies
Glioma
Cells
Glycosylation
Cell Line
Neoplasms
Competitive Binding
CHO Cells
Hybridomas
Therapeutic Uses
Glioblastoma
Heterografts
Nude Mice

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Characterization and immunotherapeutic implications for a novel antibody targeting interleukin (IL)-13 Receptor α2",
abstract = "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 (KD = 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.",
author = "Balyasnikova, {Irina V.} and Wainwright, {Derek A.} and Elena Solomaha and Gina Lee and Yu Han and Bart Thaci and Lesniak, {Maciej S.}",
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Characterization and immunotherapeutic implications for a novel antibody targeting interleukin (IL)-13 Receptor α2. / Balyasnikova, Irina V.; Wainwright, Derek A.; Solomaha, Elena; Lee, Gina; Han, Yu; Thaci, Bart; Lesniak, Maciej S.

In: Journal of Biological Chemistry, Vol. 287, No. 36, 31.08.2012, p. 30215-30227.

Research output: Contribution to journalArticle

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AU - Thaci, Bart

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