Regulatory T-cell therapy for transplantation

Abstract

As regulatory T-cell (Treg) therapy begins to enter the clinic and more clinical trials of Treg therapy are being actively planned for solid organ transplantations, a thorough quantitative assessment of therapeutic dosing is essential for the design of an effective Treg-therapy trial in the solid organ transplant setting. Considering the requirement for a high percentage of Tregs to control transplant rejection in mouse models of transplantation and the total cellularity of the human T-cell compartment, we estimate that it would take billions of Tregs, preferably alloantigen-reactive Tregs, to effectively control transplant rejection in humans. Donor dendritic cells and B cells can be used to selectively expand donor alloantigen-reactive Tregs. Recent improvements in manufacturing alloantigen-reactive Tregs demonstrate that billions of alloantigen-reactive T cells can be manufactured in short-term cultures. It is feasible to grow human alloantigen-reactive Tregs up to billions, an optimal number to achieve therapeutic efficacy. Better understanding of Treg lineage commitment and further technological investments are needed to ease the implementation and ensure consistency in Treg manufacturing.