Epstein-Barr virus–specific cytokine-induced killer cells for treatment of Epstein-Barr virus–related malignant lymphoma

Background: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-tran
Background: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context.
Methods: CIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool. CIK cells with EBV-specificity and conventional CIK cells were phenotypically and functionally analyzed. Additionally, CIK cells with EBV-specificity were applied to a patient with EBV-related PTLD rapidly progressing to highly aggressive B-cell lymphoma on a compassionate use basis after approval and agreement by the regulatory authorities.
Results: Pre-clinical analysis showed that generation of CIK cells with EBV-specificity was feasible. In vitro cytotoxicity analyses showed increased lysis of EBV-positive target cells, enhanced proliferative capacity and increased secretion of cytolytic and proinflammatory cytokines in the presence of EBV peptide-displaying target cells. In addition, 1 week after infusion of CIK cells with EBV-specificity, the patient's highly aggressive B-cell lymphoma persistently disappeared. CIK cells with EBV-specificity remained detectable for up to 32 days after infusion and infusion did not result in acute toxicity.
Discussion: The transfer of both anti-cancer potential and T-cell memory against EBV infection provided by EBV peptide-induced CIK cells might be considered a therapy for EBV-related PTLD.
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Author:Lisa-Marie Pfeffermann, Verena Pfirrmann, Sabine Hünecke, Melanie Bremm, Halvard-Björn Bönig, Hans-Michael Kvasnicka, Thomas Klingebiel, Peter Bader, Eva Rettinger
URN:urn:nbn:de:hebis:30:3-466894
DOI:http://dx.doi.org/10.1016/j.jcyt.2018.04.005
ISSN:1477-2566
ISSN:1465-3249
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29754771
Parent Title (English):Cytotherapy
Publisher:Taylor & Francis Group
Place of publication:Abington
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/05/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/07/03
Tag:Epstein-Barr virus; cytokine-induced killer cells; cytotoxic T cells; immunotherapy; lymphoma; post-transplantation lymphoproliferative disease
Volume:20
Issue:6
Pagenumber:12
First Page:839
Last Page:850
Note:
Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
HeBIS PPN:435982729
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0

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