Therapeutic targeting of the effector T-cell co-stimulatory molecule OX40

An emerging immunotherapeutic strategy for T-cell-mediated diseases is to directly target antigen-specific T cells that are responsible for the clinical effects, without causing general widespread immunosuppression. A T-cell co-stimulatory molecule, OX40, which is transiently expressed after antigen recognition, fits these criteria in several immune-mediated diseases. In vivo blockade of OX40 signalling specifically suppresses the function of recently activated autoantigen-specific T cells, leading to inhibition of autoimmune disease without severe immunosuppression. In addition, deliberate ligation of OX40 in tumour-bearing hosts enhances anticancer immunity. We discuss how targeting OX40 is potentially an ideal strategy for immune-based therapies in several human diseases.