Genetic modulation of effector cells to enhance GVL effects

Over the past few years, adoptive transfer studies, described in detail in other chapters of this book, have shown that donor T cells can be effective in the therapy of relapsed malignancy or viral infection in recipients of allogeneic hematopoietic stem-cell transplants [1,2]. Although administration of donor T cells has produced clinical benefit, it has been complicated by the frequent development of graft-versus-host disease (GVHD) due to alloreactive T cells present in the infused product. Gene transfer offers the possibility of improving such strategies by several means; infused T cells may be marked to monitor therapy, allogeneic T cells may be eradicated in the event of GVHD or other adverse events, or the function of infused T cells may be augmented by providing novel recognition properties or cytokine secretion. In this chapter we review current methodologies for gene transfer to immune system effector cells and then discuss strategies in preclinical and clinical use for using gene transfer to modulate T-cell function.