Suicide Gene Therapy for Graft-Versus-Host Disease

Abstract

In allogeneic hematopoietic stem cell transplantation, donor-derived T cells are key players for early immune reconstitution and efficient engraftment, as well as the graft-versus-leukemia and graft-versus-infection effects. However, a severe and quite common life-threatening complication is the development of graft-versus-host disease, during which the alloreactive donor T cells attack the host. Controlling graft-versus-host disease while preserving the benefits of graft-versus-leukemia still constitutes a challenge. A promising approach for the control of graft-versus-host disease is suicide gene therapy, which involves the ex vivo genetic modification of donor T cells with a suicide gene that allows for the selective elimination of the cells in vivo if graft-versus-host disease occurs. This article presents an overview of such approaches with special reference to lessons learned from previous clinical experiences, as well as a discussion of critical factors in suicide gene therapy.

KEYWORDS::

• allogeneic stem cell transplantation
• cytosine deaminase
• donor lymphocyte infusion
• graft-versus-host disease
• graft-versus-infection
• graft-versus-leukemia
• herpes simplex virus thymidine kinase
• selection marker
• suicide gene therapy

Financial & competing interests disclosure

The research in the authors‘ laboratory is supported by the Swedish Childhood Cancer Foundation, Clinigene NoE (FP6) and the Vinnova foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The research in the authors‘ laboratory is supported by the Swedish Childhood Cancer Foundation, Clinigene NoE (FP6) and the Vinnova foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.