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Exhausting alloreactivity of donor-derived CAR T cells

A study in mouse models of allogeneic stem cell transplantation with donor-derived CD19 chimeric antigen receptor (CAR) T cells for the treatment of relapsed B cell malignancies indicates that T cell exhaustion might have a role in preventing allogeneic reactivity of CD19 CAR T cells.

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Figure 1: Ghosh et al.6 show in mouse models of allogeneic stem cell transplant of donor-matched CD19 CAR T cells for the treatment of B cell malignancies that excessive stimulation of alloreactive CD19 CAR T cells through cumulative CAR and TCR signaling via STAT and MAPK upregulates inhibitory receptors and pro-apoptotic molecules such as PD-1, Fas and FasL.

Marina Corral Spence/Springer Nature

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Correspondence to Helen E Heslop.

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Competing interests

H.E.H. has received research funding from Celgene for studies of genetically modified T cells. M.M. has no conflicts to declare.

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Mamonkin, M., Heslop, H. Exhausting alloreactivity of donor-derived CAR T cells. Nat Med 23, 147–148 (2017). https://doi.org/10.1038/nm.4276

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