Adoptive transfer of antigen-specific T-cells of donor type for immunotherapy of viral infections following allogeneic hematopoietic cell transplants

Abstract

Allogeneic marrow and cytokine-mobilized peripheral blood stem cells adequately depleted of T cells prevent acute and chronic forms of graft versus host disease in HLA-matched and non-identical hosts without any posttransplant immunosuppressive prophylaxis. Current cytoreductive regimens secure consistent durable engraftment, and full donor chimerism. The risk of relapse following such transplants in patients with AML and ALL has been low, and not different from that recorded following unmodified transplants. However, in HLA-disparate hosts the risk of infections caused by EBV, CMV, and certain fungi are increased. To address this limitation, others and we are exploring adoptive immunotherapies with in vitro generated, pathogen-specific T cells. Early clinical trials already indicate the potential of such T cells to treat and prevent life threatening diseases caused by these pathogens, particularly in recipients of T cell depleted grafts who do not require ongoing treatment with immunosuppressive agents, and therefore provide a permissive environment for the expansion and persistence of the T cells following adoptive transfer. New more predictable strategies are under development, which should allow such therapies to be broadly applicable.