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

• Published in: Frontiers in immunology 2018-06, Vol.9, p.1475-1475
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: adoptive T cell therapy; Epstein–Barr virus; Immunology; posttransplant lymphoproliferative disease; T cell receptor sequencing; transplantation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.01475

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.