An interleukin 13 receptor α 2-specific peptide homes to human Glioblastoma multiforme xenografts.

Abstract

Interleukin 13 receptor α 2 (IL-13Rα2) is a glioblastoma multiforme (GBM)-associated plasma membrane receptor, a brain tumor of dismal prognosis. Here, we isolated peptide ligands for IL-13Rα2 with use of a cyclic disulphide-constrained heptapeptide phages display library and 2 in vitro biopanning schemes with GBM cells that do (G26-H2 and SnB19-pcDNA cells) or do not (G26-V2 and SnB19-asIL-13Rα2 cells) over-express IL-13Rα2. We identified 3 peptide phages that bind to IL-13Rα2 in cellular and protein assays. One of the 3 peptide phages, termed Pep-1, bound to IL-13Rα2 with the highest specificity, surprisingly, also in a reducing environment. Pep-1 was thus synthesized and further analyzed in both linear and disulphide-constrained forms. The linear peptide bound to IL-13Rα2 more avidly than did the disulphide-constrained form and was efficiently internalized by IL-13Rα2-expressing GBM cells. The native ligand, IL-13, did not compete for the Pep-1 binding to the receptor and vice versa in any of the assays, indicating that the peptide might be binding to a site on the receptor different from the native ligand. Furthermore, we demonstrated by noninvasive near infrared fluorescence imaging in nude mice that Pep-1 binds and homes to both subcutaneous and orthotopic human GBM xenografts expressing IL-13Rα2 when injected by an intravenous route. Thus, we identified a linear heptapeptide specific for the IL-13Rα2 that is capable of crossing the blood-brain tumor barrier and homing to tumors. Pep-1 can be further developed for various applications in cancer and/or inflammatory diseases.

• Authors: Hetal Pandya, Denise M Gibo, Shivank Garg, Steven Kridel, Waldemar Debinski
• Journal: Neuro-oncology (Neuro Oncol) Vol. 14 Issue 1 Pg. 6-18 (Jan 2012) ISSN: 1523-5866 [Electronic] England
• PMID: 21946118 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-13 Receptor alpha2 Subunit
• Peptide Library
• Peptides

Topics

• Animals
• Binding, Competitive
• Blood-Brain Barrier
• Brain Neoplasms (metabolism)
• Female
• Glioblastoma (metabolism)
• Humans
• Interleukin-13 Receptor alpha2 Subunit (metabolism)
• Mice
• Mice, Nude
• Peptide Library
• Peptides (pharmacokinetics)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays