Novel application of lentiviral vectors towards treatment of graft-versus-host disease

• Published in: Expert opinion on biological therapy Vol. 9; no. 6; p. 749
• Main Authors: Scaife, Matthew D, Neschadim, Anton, Fowler, D H, Medin, J A
• Format: Journal Article
• Language: English
• Published: England 01-06-2009
• Subjects: Cell Lineage; Genetic Therapy; Genetic Vectors; Graft vs Host Disease - prevention & control; Graft vs Host Disease - therapy; Hematopoietic Stem Cell Transplantation; Humans; Lentivirus - genetics; Transplantation, Homologous
• ISSN: 1744-7682
• DOI: 10.1517/14712590903002021

Allogeneic transplantation of hematopoietic stem cells and lymphocytes is a curative treatment for malignant and non-malignant disease. However, the primary complication limiting the safety of transplantation is graft-versus-host disease (GvHD), which is mediated by donor T cells. Strategies for pre- and post-transplant manipulation of graft cells are not yet optimal for balancing GvHD severity with beneficial Graft-versus-Leukemia (GvL) effects. Emerging cell fate control gene therapy (CFCGT)-based strategies, such as 'suicide' gene therapy for donor T cell regulation, can supplement existing transplantation approaches by providing a safety element to reduce GvHD. Past uses of CFCGT in the clinic have provided proof-of-principle that GvHD can be controlled by such a strategy. However, there exists a need for improved transgene delivery and suicide control systems. Recently, lentiviral vectors (LVs) have emerged as effective gene delivery vehicles for the clinic. Combining lentiviral gene delivery with newer generations of 'suicide' systems that possess improved enzyme/prodrug specificities, activities, and reduced immunogenicity, could provide the necessary degree of control required to more successfully manage GvHD. Improving the safety of transplantation through successful CFCGT will serve to expand the potential donor pool and the spectrum of disorders that can be treated by this therapeutic schema.