Cargando…
Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease
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 leadin...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030255/ https://www.ncbi.nlm.nih.gov/pubmed/29997626 http://dx.doi.org/10.3389/fimmu.2018.01475 |
_version_ | 1783337110255697920 |
---|---|
author | Schultze-Florey, Rebecca E. Tischer, Sabine Kuhlmann, Leonie Hundsdoerfer, Patrick Koch, Arend Anagnostopoulos, Ioannis Ravens, Sarina Goudeva, Lilia Schultze-Florey, Christian Koenecke, Christian Blasczyk, Rainer Koehl, Ulrike Heuft, Hans-Gert Prinz, Immo Eiz-Vesper, Britta Maecker-Kolhoff, Britta |
author_facet | Schultze-Florey, Rebecca E. Tischer, Sabine Kuhlmann, Leonie Hundsdoerfer, Patrick Koch, Arend Anagnostopoulos, Ioannis Ravens, Sarina Goudeva, Lilia Schultze-Florey, Christian Koenecke, Christian Blasczyk, Rainer Koehl, Ulrike Heuft, Hans-Gert Prinz, Immo Eiz-Vesper, Britta Maecker-Kolhoff, Britta |
author_sort | Schultze-Florey, Rebecca E. |
collection | PubMed |
description | 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, epitope spreading to unrelated EBV antigens occurred suggesting onset of endogenous T-cell production, which was supported by detection of recipient-derived clones in NGS TCR-profiling. Continuous complete remission was confirmed 27 months after initial diagnosis. |
format | Online Article Text |
id | pubmed-6030255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60302552018-07-11 Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease Schultze-Florey, Rebecca E. Tischer, Sabine Kuhlmann, Leonie Hundsdoerfer, Patrick Koch, Arend Anagnostopoulos, Ioannis Ravens, Sarina Goudeva, Lilia Schultze-Florey, Christian Koenecke, Christian Blasczyk, Rainer Koehl, Ulrike Heuft, Hans-Gert Prinz, Immo Eiz-Vesper, Britta Maecker-Kolhoff, Britta Front Immunol Immunology 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, epitope spreading to unrelated EBV antigens occurred suggesting onset of endogenous T-cell production, which was supported by detection of recipient-derived clones in NGS TCR-profiling. Continuous complete remission was confirmed 27 months after initial diagnosis. Frontiers Media S.A. 2018-06-27 /pmc/articles/PMC6030255/ /pubmed/29997626 http://dx.doi.org/10.3389/fimmu.2018.01475 Text en Copyright © 2018 Schultze-Florey, Tischer, Kuhlmann, Hundsdoerfer, Koch, Anagnostopoulos, Ravens, Goudeva, Schultze-Florey, Koenecke, Blasczyk, Koehl, Heuft, Prinz, Eiz-Vesper and Maecker-Kolhoff. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Schultze-Florey, Rebecca E. Tischer, Sabine Kuhlmann, Leonie Hundsdoerfer, Patrick Koch, Arend Anagnostopoulos, Ioannis Ravens, Sarina Goudeva, Lilia Schultze-Florey, Christian Koenecke, Christian Blasczyk, Rainer Koehl, Ulrike Heuft, Hans-Gert Prinz, Immo Eiz-Vesper, Britta Maecker-Kolhoff, Britta Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease |
title | Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease |
title_full | Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease |
title_fullStr | Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease |
title_full_unstemmed | Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease |
title_short | Dissecting Epstein-Barr Virus-Specific T-Cell Responses After Allogeneic EBV-Specific T-Cell Transfer for Central Nervous System Posttransplant Lymphoproliferative Disease |
title_sort | dissecting epstein-barr virus-specific t-cell responses after allogeneic ebv-specific t-cell transfer for central nervous system posttransplant lymphoproliferative disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030255/ https://www.ncbi.nlm.nih.gov/pubmed/29997626 http://dx.doi.org/10.3389/fimmu.2018.01475 |
work_keys_str_mv | AT schultzefloreyrebeccae dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT tischersabine dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT kuhlmannleonie dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT hundsdoerferpatrick dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT kocharend dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT anagnostopoulosioannis dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT ravenssarina dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT goudevalilia dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT schultzefloreychristian dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT koeneckechristian dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT blasczykrainer dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT koehlulrike dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT heufthansgert dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT prinzimmo dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT eizvesperbritta dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease AT maeckerkolhoffbritta dissectingepsteinbarrvirusspecifictcellresponsesafterallogeneicebvspecifictcelltransferforcentralnervoussystemposttransplantlymphoproliferativedisease |