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

Kathryn Kline, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Wengen Chen, Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Michael E. Kallen, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
Rima Koka, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
Destiny Omili, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Xiaoxuan Fan, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Thierry Iraguha, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Etse Gebru, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Nishanthini Dishanthan, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Jillian M. Baker, Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
Kenneth A. Dietze, Department of Microbiology and Immunology, University of Maryland, Baltimore, MD, USA.
Jean A. Yared, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Kim Hankey, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Saurabh Dahiya, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Silke V. Niederhaus, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Kieron Dunleavy, Hematology Program, George Washington University, Washington, DC, USA.
Nancy M. Hardy, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Tim Luetkens, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Aaron P. Rapoport, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
Djordje Atanackovic, University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.

Document Type

Journal Article

Publication Date

8-1-2023

Journal

Human vaccines & immunotherapeutics

Volume

19

Issue

2

DOI

10.1080/21645515.2023.2216116

Keywords

B cell lymphoma; CAR-T cells; Post-transplant lymphoproliferative disorder; T cells; immunosuppression; immunotherapy; kidney transplant

Abstract

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.

Department

Medicine

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