Chimeric antigen receptor (CAR) T cells for the treatment of a kidney transplant patient with post-transplant lymphoproliferative disorder (PTLD)
Human vaccines & immunotherapeutics
B cell lymphoma; CAR-T cells; Post-transplant lymphoproliferative disorder; T cells; immunosuppression; immunotherapy; kidney transplant
Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication following kidney transplantation, and there is a critical and unmet need for PTLD treatments associated with more pronounced and durable responses. To date, reports on the use of CD19-targeted chimeric antigen receptor (CAR) T (CAR-T) cells in patients after solid organ transplant (SOT) have been anecdotal, clinical presentations and outcomes have been heterogenous, and a longitudinal analysis of CAR-T cell expansion and persistence in PTLD patients has not been reported. Our report describes a patient with a history of renal transplant who received CD19-directed CAR-T cell therapy for the treatment of refractory PTLD, diffuse large B cell lymphoma (DLBCL)-type. We show that even with the background of prolonged immunosuppression for SOT, it is possible to generate autologous CAR-T products capable of expansion and persistence in vivo, without evidence of excess T-cell exhaustion. Our data indicate that CAR-T cells generated from a SOT recipient with PTLD can yield deep remissions without increased toxicity or renal allograft dysfunction. Future clinical studies should build on these findings to investigate CAR-T therapy, including longitudinal monitoring of CAR-T phenotype and function, for PTLD in SOT recipients.
Kline, Kathryn; Chen, Wengen; Kallen, Michael E.; Koka, Rima; Omili, Destiny; Fan, Xiaoxuan; Iraguha, Thierry; Gebru, Etse; Dishanthan, Nishanthini; Baker, Jillian M.; Dietze, Kenneth A.; Yared, Jean A.; Hankey, Kim; Dahiya, Saurabh; Niederhaus, Silke V.; Dunleavy, Kieron; Hardy, Nancy M.; Luetkens, Tim; Rapoport, Aaron P.; and Atanackovic, Djordje, "Chimeric antigen receptor (CAR) T cells for the treatment of a kidney transplant patient with post-transplant lymphoproliferative disorder (PTLD)" (2023). GW Authored Works. Paper 2668.