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 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01475

DOI=10.3389/fimmu.2018.01475

ISSN=1664-3224

ABSTRACT=EBV-associated post-transplant lymphoproliferative disease (PTLD) with 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 ten 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 three months. Due to the poor prognosis of CNS PTLD and lack of EBV-specific T-cells 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-specific T-cells from a 5/10 HLA–matched unrelated third party donor. No relevant acute toxicity was observed. EBV-specific T-cells became detectable after first injection and increased during the treatment course. 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.