TALEN-mediated genetic inactivation of the glucocorticoid receptor in cytomegalovirus-specific T cells

Menger L (2015) Blood (Link to abstract)

T-cells control Cytomegalovirus (CMV) infection/ reactivation after allogeneic hematopoietic stem cell transplantation (HSCT). T- cell therapy can be used to control CMV replication after HSCT but patients with graft-versus-host disease (GVHD) on steroids are usually not given this treatment due to the fear of suppression and inactivation of transferred T cells by steroids. Genetic disruption using electroporation of transcription activator–like effector nuclease (TALEN) messenger RNA was used by the authors to interfere with the glucocorticoid receptor (GR) gene on T cells. In vitro assays showed that CMV-specific CD8+ T cells retained specific killing of target cells.

* This report provides evidence that manipulation of the glucocorticoid receptor of genetically engineered T cells could induce resistance to steroids of these cells and therefore overcome the issues with glucocorticoid treatment and T cell therapies.