Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative Disorders

Post-transplant lymphoproliferative disorders (PTLD) represent a life-threatening complication following solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with relapsed or refractory (R/R) disease, where therapeutic options...

Full description

Saved in:
Bibliographic Details
Main Authors: Martina Canichella, Paolo de Fabritiis
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Antibodies
Subjects:
Online Access:https://www.mdpi.com/2073-4468/14/2/47
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850156851035897856
author Martina Canichella
Paolo de Fabritiis
author_facet Martina Canichella
Paolo de Fabritiis
author_sort Martina Canichella
collection DOAJ
description Post-transplant lymphoproliferative disorders (PTLD) represent a life-threatening complication following solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with relapsed or refractory (R/R) disease, where therapeutic options are limited and prognosis is poor. Among emerging strategies, adoptive cellular immunotherapy—specifically Epstein–Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)—significantly improved outcomes in this challenging patient population. EBV-CTLs restore virus-specific immunity and induce sustained remissions with minimal toxicity, even in heavily pretreated individuals. The most promising cellular product to date is tabelecleucel, an off-the-shelf, allogeneic EBV-specific T-cell therapy, which is currently the only cellular therapy approved by the European Medicines Agency (EMA) for the treatment of R/R EBV-positive PTLD following SOT or allo-HSCT. This review aims to provide an overview of PTLD treatment with a specific focus on adoptive cellular immunotherapy. We highlight the most robust clinical outcomes reported with EBV-CTLs, particularly those achieved with tabelecleucel, and explore emerging cellular approaches such as CAR T-cell therapy, which may further broaden therapeutic strategies in the near future.
format Article
id doaj-art-bb123b7e553a4bec848d14decadcf0c7
institution OA Journals
issn 2073-4468
language English
publishDate 2025-06-01
publisher MDPI AG
record_format Article
series Antibodies
spelling doaj-art-bb123b7e553a4bec848d14decadcf0c72025-08-20T02:24:22ZengMDPI AGAntibodies2073-44682025-06-011424710.3390/antib14020047Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative DisordersMartina Canichella0Paolo de Fabritiis1Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, ItalyHematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, ItalyPost-transplant lymphoproliferative disorders (PTLD) represent a life-threatening complication following solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with relapsed or refractory (R/R) disease, where therapeutic options are limited and prognosis is poor. Among emerging strategies, adoptive cellular immunotherapy—specifically Epstein–Barr virus-specific cytotoxic T lymphocytes (EBV-CTLs)—significantly improved outcomes in this challenging patient population. EBV-CTLs restore virus-specific immunity and induce sustained remissions with minimal toxicity, even in heavily pretreated individuals. The most promising cellular product to date is tabelecleucel, an off-the-shelf, allogeneic EBV-specific T-cell therapy, which is currently the only cellular therapy approved by the European Medicines Agency (EMA) for the treatment of R/R EBV-positive PTLD following SOT or allo-HSCT. This review aims to provide an overview of PTLD treatment with a specific focus on adoptive cellular immunotherapy. We highlight the most robust clinical outcomes reported with EBV-CTLs, particularly those achieved with tabelecleucel, and explore emerging cellular approaches such as CAR T-cell therapy, which may further broaden therapeutic strategies in the near future.https://www.mdpi.com/2073-4468/14/2/47PTLD—post-transplant lymphoproliferative disordersRIS—reduction in immunosuppressionEBV—Epstein–Barr virusallo-HSCT—allogeneic stem cell transplantation
spellingShingle Martina Canichella
Paolo de Fabritiis
Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative Disorders
Antibodies
PTLD—post-transplant lymphoproliferative disorders
RIS—reduction in immunosuppression
EBV—Epstein–Barr virus
allo-HSCT—allogeneic stem cell transplantation
title Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative Disorders
title_full Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative Disorders
title_fullStr Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative Disorders
title_full_unstemmed Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative Disorders
title_short Adoptive Cell Immunotherapy in Relapse/Refractory Epstein–Barr Virus-Driven Post-Transplant Lymphoproliferative Disorders
title_sort adoptive cell immunotherapy in relapse refractory epstein barr virus driven post transplant lymphoproliferative disorders
topic PTLD—post-transplant lymphoproliferative disorders
RIS—reduction in immunosuppression
EBV—Epstein–Barr virus
allo-HSCT—allogeneic stem cell transplantation
url https://www.mdpi.com/2073-4468/14/2/47
work_keys_str_mv AT martinacanichella adoptivecellimmunotherapyinrelapserefractoryepsteinbarrvirusdrivenposttransplantlymphoproliferativedisorders
AT paolodefabritiis adoptivecellimmunotherapyinrelapserefractoryepsteinbarrvirusdrivenposttransplantlymphoproliferativedisorders