Chimeric antigen receptor (CAR) T cells for the treatment of a kidney transplant patient with post-transplant lymphoproliferative disorder (PTLD)

• Published in: Human vaccines & immunotherapeutics Vol. 19; no. 2; p. 2216116
• Main Authors: 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, Atanackovic, Djordje
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.08.2023; Taylor & Francis Group
• Subjects: b cell lymphoma; car-t cells; Case Report; Humans; immunosuppression; immunotherapy; Immunotherapy - Other; kidney transplant; Kidney Transplantation - adverse effects; Lymphoproliferative Disorders - etiology; Lymphoproliferative Disorders - therapy; Organ Transplantation - adverse effects; post-transplant lymphoproliferative disorder; Receptors, Chimeric Antigen - therapeutic use; t cells; T-Lymphocytes - pathology; B cell lymphoma; CAR-T cells; immunotherapy; kidney transplant; Post-transplant lymphoproliferative disorder; immunosuppression; T cells
• ISSN: 2164-5515; 2164-554X
• DOI: 10.1080/21645515.2023.2216116

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.