Scientific Publications by FDA Staff
Hum Gene Ther Methods 2012 Apr;23(2):137-47
Specific Targeting of Human Interleukin (IL)-13 Receptor alpha2-Positive Cells with Lentiviral Vectors Displaying IL-13.
Ou W, Marino MP, Suzuki A, Joshi B, Husain SR, Maisner A, Galanis E, Puri RK, Reiser J
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 alpha2 (IL-13Ralpha2) is uniquely overexpressed in many different human tumors, making it an attractive target for cancer therapy. In this study, we examined whether IL-13Ralpha2-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-13Ralpha2, but not cells expressing low levels of IL-13Ralpha2 in vitro. In vivo, it specifically targeted IL-13Ralpha2-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.
|Category: Journal Article|
|PubMed ID: #22612657||DOI: 10.1089/hgtb.2012.054|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2012-05-24||Entry Last Modified: 2013-01-06|