T cells expressing chimeric antigen receptor promote immune tolerance. JCI insight Pierini, A. n., Iliopoulou, B. P., Peiris, H. n., Pérez-Cruz, M. n., Baker, J. n., Hsu, K. n., Gu, X. n., Zheng, P. P., Erkers, T. n., Tang, S. W., Strober, W. n., Alvarez, M. n., Ring, A. n., Velardi, A. n., Negrin, R. S., Kim, S. K., Meyer, E. H. 2017; 2 (20)


Cellular therapies based on permanent genetic modification of conventional T cells have emerged as a promising strategy for cancer. However, it remains unknown if modification of T cell subsets, such as Tregs, could be useful in other settings, such as allograft transplantation. Here, we use a modular system based on a chimeric antigen receptor (CAR) that binds covalently modified mAbs to control Treg activation in vivo. Transient expression of this mAb-directed CAR (mAbCAR) in Tregs permitted Treg targeting to specific tissue sites and mitigated allograft responses, such as graft-versus-host disease. mAbCAR Tregs targeted to MHC class I proteins on allografts prolonged islet allograft survival and also prolonged the survival of secondary skin grafts specifically matched to the original islet allograft. Thus, transient genetic modification to produce mAbCAR T cells led to durable immune modulation, suggesting therapeutic targeting strategies for controlling alloreactivity in settings such as organ or tissue transplantation.

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