T cell immunotherapy for immune reconstitution and GVHD prevention after allogeneic hematopoietic stem cell transplantation

Many different studies have demonstrated that early recovery of the adaptive immune system after allogeneic hematopoietic stem cell transplantation (HSCT) is predominantly sustained by peripheral expansion of donor-derived, mature lymphocytes transferred with the graft. Different approaches based on the infusion of donor T cells after HSCT have been developed mainly to accelerate immune recovery and to treat/prevent (a) malignancy recurrence, (b) life-threatening infections, and (c) immune-mediated disorders, such as graft-versus-host disease (GVHD). For many years, donor lymphocyte infusion (DLI) has been a widely used approach to prevent and to treat leukemia recurrence, to convert mixed chimerism into complete donor chimerism, and to accelerate immune reconstitution of patients after HSCT. More sophisticated strategies of adoptive infusion of T cell lines/clones capable of mediating a graft-versus-leukemia (GVL) response, while avoiding GVHD occurrence, or specific for the most life-threatening pathogens (e.g., cytomegalovirus, Epstein-Barr virus, and adenovirus) have been envisaged and successfully tested in pilot trials in the early post-transplantation period. Also, ex vivo expanded regulatory T (Treg) cells have been shown to be beneficial for preventing GVHD post-HSCT. In this review, we will focus on DLI as well as more complex cellular therapies that require extensive cell manipulation.