Specific targeting of human interleukin (IL)-13 receptor α2-positive cells with lentiviral vectors displaying IL-13

Wu Ou, Michael P. Marino, Akiko Suzuki, Bharat Joshi, Syed R. Husain, Andrea Maisner, Evanthia Galanis, Raj K. Puri, Jakob Reiser

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The ability to selectively and efficiently target transgene delivery to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. Lentiviral vectors have several advantages that make them attractive as gene delivery vehicles and their tropism can be altered through pseudotyping, allowing transgene delivery to specific populations of cells. The human interleukin-13 receptor α2 (IL-13Rα2) is uniquely overexpressed in many different human tumors, making it an attractive target for cancer therapy. In this study, we examined whether IL-13Rα2-positive tumor cells can be specifically targeted with lentiviral vector pseudotypes containing a truncated fusion (F) protein derived from measles virus (MV) and a tail-truncated and receptor-blind MV hemagglutinin (H) protein bearing IL-13 at the C terminus. The retargeted lentiviral vector efficiently transduced cells that express high levels of IL-13Rα2, but not cells expressing low levels of IL-13Rα2 in vitro. In vivo, it specifically targeted IL-13Rα2-positive glioma cell xenografts in immunodeficient mice in the context of subcutaneous and intracranial glioma models. Similar lentiviral vectors may be developed for targeting other tumors expressing specific cell surface receptors.

Original languageEnglish (US)
Pages (from-to)137-147
Number of pages11
JournalHuman Gene Therapy Methods
Volume23
Issue number2
DOIs
StatePublished - Apr 1 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Applied Microbiology and Biotechnology
  • Genetics
  • Pharmacology
  • Genetics(clinical)

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