Now or never? The case for cell-based immunosuppression in kidney transplantation

• Published in: Kidney international Vol. 87; no. 6; pp. 1116 - 1124
• Main Authors: Hutchinson, James A., Geissler, Edward K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2015; Elsevier Limited
• Subjects: Animals; Calcineurin Inhibitors - adverse effects; cell therapy; Cell- and Tissue-Based Therapy - adverse effects; Graft Rejection - immunology; Graft Rejection - prevention & control; Humans; Immunosuppression - methods; Kidney Transplantation; Mreg; Mreg_UKR; T-Lymphocytes, Regulatory - immunology; The ONE Study; Thymus Gland - cytology; Mreg; The ONE Study; cell therapy; Mreg_UKR
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2015.50

By exploiting mechanisms of immunological regulation against donor alloantigen, it may be possible to reduce the dependence of kidney transplant recipients upon calcineurin inhibitor-based maintenance immunosuppression. One means to strengthen regulatory responses is treating recipients with preparations of regulatory cells obtained by ex vivo manipulation. This strategy, which is a well-established experimental method, has been developed to the point that early-phase clinical trials in kidney transplantation are now feasible. Cell-based therapies represent a radical departure from conventional treatment, so what grounds are there for this new approach? This article offers a three-part justification for trialing cell-based therapies in kidney transplantation: first, a clinical need for alternatives to standard immunosuppression is identified, based on the inadequacies of calcineurin inhibitor-based regimens in preventing late allograft loss; second, a mechanistic explanation of how cell-based therapies might address this clinical need is given; and third, the possible benefit to patients is weighed against the potential risks of cell-based immunosuppressive therapy. It is concluded that the safety of cell-based immunosuppressive therapy will not be greatly improved by further basic scientific and preclinical development. Only trials in humans can now tell us whether cell-based therapy is likely to benefit kidney transplant recipients, but these should be conservative in design to minimize any potential harm to patients.