Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease

Frontiers in Immunology
Rebecca E Schultze-FloreyBritta Maecker-Kolhoff

Abstract

Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) with central nervous system (CNS) involvement is a severe complication after solid organ transplantation. Standard treatment with reduction of immunosuppression and anti-CD20 antibody application often fails leading to poor outcome. Here, we report the case of an 11-year-old boy with multilocular EBV-positive CNS PTLD 10 years after liver transplantation. Complete remission was achieved by repeated intravenous and intrathecal anti-CD20 antibody rituximab administration combined with intrathecal chemotherapy (methotrexate, cytarabine, prednisone) over a time period of 3 months. Due to the poor prognosis of CNS PTLD and lack of EBV-specific T-cells (EBV-CTLs) in patient's blood, we decided to perform EBV-directed T-cell immunotherapy as a consolidating treatment. The patient received five infusions of allogeneic EBV-CTLs from a 5/10 HLA-matched unrelated third-party donor. No relevant acute toxicity was observed. EBV-CTLs became detectable after first injection and increased during the treatment course. Next-generation sequencing (NGS) TCR-profiling verified the persistence and expansion of donor-derived EBV-specific clones. After two transfers,...Continue Reading

References

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Citations

Apr 3, 2020·Journal of Translational Medicine·Nele Carolin HeinemannBritta Eiz-Vesper
Nov 7, 2019·The Journal of Clinical Investigation·Susan ProckopRichard J O'Reilly
Feb 6, 2021·Current Hematologic Malignancy Reports·Francesca Montanari, Manuela Orjuela-Grimm

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Methods Mentioned

BETA
FACS
PCR
biopsy
flow cytometry

Software Mentioned

VDJtools
package
tcR

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