The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells

Transplantation” and involves scientists from Germany, France, Italy, the United Kingdom and the United States with the aim of improving treatment and the overall quality of life for kidney transplant patients through cell therapy. The goal of the project is to develop and test an array of novel manufactured cell therapy products that have promise to reduce a transplant patient’s life-long dependency on immunosuppressive drugs. In principle, the hypothesis behind cell therapy in the context of organ transplantation is that treating recipients with a concentrated dose of well-defined regulatory immune cells near the time of transplantation will trigger a selfsustaining immune regulation that establishes a level of functional protection against allograft destruction. This concept is fundamentally different from other modes of treatment for transplant recipients since the therapy supplements, or ‘adds-in’, a functional cellular component of the immune system that is believed capable of precipitating and establishing a protective immunological balance favoring allograft survival. In contrast, all other current forms of therapy seek to take away immune function through depletion of classes of detrimental immune cells, or through blockage of signals in these cells required for immune reactions; this form of ‘functionally inhibitory’ therapy primarily causes a general suppression of the immune system. The ONE Study consortium explores the feasibility and potential of cell therapy in organ transplantation by bringing together experts to test different regulatory cell products composed of specific T cell (T regulatory cell, Treg and T regulatory type 1 cell, Tr1 cell), dendritic cell and macrophage subpopulations. While the primary objective of the study is to perform a stringent side-byside comparison of these cell products using a single (ONE) standardized trial protocol, a secondary aim is to use this unique cooperative opportunity to experimentally examine the immunoregulatory characteristics of the cell products to be tested.