Co-stimulation Blockade Plus T-Cell Depletion in Transplant Patients: Towards a Steroid- and Calcineurin Inhibitor-Free Future?

Long-term survival of solid allografts depends on both immunosuppressive efficacy and reducing the side effects associated with these therapies. Immunotherapies developed over the past 15 years to prevent organ rejection have greatly improved cardiovascular and renal function compared with classical therapies, such as calcineurin inhibitors and corticosteroids. Immunotherapies that target T cells through the co-stimulation blockade (CTLA-4-Ig) improve renal function and the survival of grafts and patients, but are associated with higher rates of T-cell-mediated acute rejection. Improvements to safe and efficacious therapeutic options could combine a co-stimulation blockade with a depleting immunotherapy. Herein, we describe the clinical outcomes and the likely causes of defects in the co-stimulation blockade, and comment on new therapeutic strategies to overcome these. Great progress has been made to optimize immunotherapy using the co-stimulation blockade, but the therapeutic combinations should be assessed further.