TY  - JOUR
A1  - Pfeffermann, Lisa-Marie
A1  - Pfirrmann, Verena
A1  - Hünecke, Sabine
A1  - Bremm, Melanie
A1  - Bönig, Halvard-Björn
A1  - Kvasnicka, Hans Michael
A1  - Klingebiel, Thomas
A1  - Bader, Peter
A1  - Rettinger, Eva
T1  - Epstein-Barr virus–specific cytokine-induced killer cells for treatment of Epstein-Barr virus–related malignant lymphoma
T2  - Cytotherapy
N2  - 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.
KW  - cytokine-induced killer cells
KW  - cytotoxic T cells
KW  - Epstein-Barr virus
KW  - immunotherapy
KW  - lymphoma
KW  - post-transplantation lymphoproliferative disease
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46689
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-466894
SN  - 1477-2566
SN  - 1465-3249
N1  - 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/).
VL  - 20
IS  - 6
SP  - 839
EP  - 850
PB  - Elsevier
CY  - Amsterdam
ER  -