Reconstitution of EBV-directed T cell immunity by adoptive transfer of peptide-stimulated T cells in a patient after allogeneic stem cell transplantation for AITL.

Autor: Lammoglia Cobo MF; Department of Hematology, Oncology, and Tumor Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Ritter J; Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Gary R; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Seitz V; Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; HS Diagnomics GmbH, Berlin, Germany., Mautner J; Department of Medicine III, LMU-Klinikum, Munich, Germany.; German Centre for Infection Research, Munich, Germany., Aigner M; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Völkl S; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Schaffer S; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Moi S; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Seegebarth A; Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Bruns H; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Rösler W; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Amann K; Department of Nephropathology, Institute of Pathology, University of Erlangen, Erlangen, Germany., Büttner-Herold M; Department of Nephropathology, Institute of Pathology, University of Erlangen, Erlangen, Germany., Hennig S; HS Diagnomics GmbH, Berlin, Germany., Mackensen A; Department of Internal Medicine 5 -Hematology/Oncology, University Hospital Erlangen, Erlangen, Germany., Hummel M; Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Moosmann A; Department of Medicine III, LMU-Klinikum, Munich, Germany.; German Centre for Infection Research, Munich, Germany., Gerbitz A; Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2022 Apr 22; Vol. 18 (4), pp. e1010206. Date of Electronic Publication: 2022 Apr 22 (Print Publication: 2022).
DOI: 10.1371/journal.ppat.1010206
Abstrakt: Reconstitution of the T cell repertoire after allogeneic stem cell transplantation is a long and often incomplete process. As a result, reactivation of Epstein-Barr virus (EBV) is a frequent complication that may be treated by adoptive transfer of donor-derived EBV-specific T cells. We generated donor-derived EBV-specific T cells by stimulation with peptides representing defined epitopes covering multiple HLA restrictions. T cells were adoptively transferred to a patient who had developed persisting high titers of EBV after allogeneic stem cell transplantation for angioimmunoblastic T-cell lymphoma (AITL). T cell receptor beta (TCRβ) deep sequencing showed that the T cell repertoire of the patient early after transplantation (day 60) was strongly reduced and only very low numbers of EBV-specific T cells were detectable. Manufacturing and in vitro expansion of donor-derived EBV-specific T cells resulted in enrichment of EBV epitope-specific, HLA-restricted T cells. Monitoring of T cell clonotypes at a molecular level after adoptive transfer revealed that the dominant TCR sequences from peptide-stimulated T cells persisted long-term and established an EBV-specific TCR clonotype repertoire in the host, with many of the EBV-specific TCRs present in the donor. This reconstituted repertoire was associated with immunological control of EBV and with lack of further AITL relapse.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AMo receives project funding from Biosyngen Pte. Ltd. for preclinical development of EBV-specific TCRs not related to this study.
Databáze: MEDLINE
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