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July 2021; 8 (4) ArticleOpen Access

Allogeneic BK Virus-Specific T-Cell Treatment in 2 Patients With Progressive Multifocal Leukoencephalopathy

Franziska Hopfner, Nora Möhn, Britta Eiz-Vesper, Britta Maecker-Kolhoff, Jens Gottlieb, Rainer Blasczyk, Nima Mahmoudi, Kaweh Pars, Ortwin Adams, Martin Stangel, Mike P. Wattjes, Günter Höglinger, Thomas Skripuletz
First published May 17, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001020
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Article Information

vol. 8 no. 4 e1020
DOI: 
https://doi.org/10.1212/NXI.0000000000001020
PubMed: 
34001660
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received January 10, 2021
  • Accepted in final form March 29, 2021
  • First Published May 17, 2021.
Copyright & Usage: 
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Author Disclosures

    1. Franziska Hopfner, MD,
    2. Nora Möhn, MD (moehn.nora{at}mh-hannover.de),
    3. Britta Eiz-Vesper, PhD (eiz-vesper.britta{at}mh-hannover.de),
    4. Britta Maecker-Kolhoff, MD (maecker.britta{at}mh-hannover.de),
    5. Jens Gottlieb, MD (gottlieb.jens{at}mh-hannover.de),
    6. Rainer Blasczyk, MD (blasczyk.rainer{at}mh-hannover.de),
    7. Nima Mahmoudi, MD (mahmoudi.nima{at}mh-hannover.de),
    8. Kaweh Pars, MD (kaweh.pars{at}uni-oldenburg.de),
    9. Ortwin Adams, MD, PhD (ortwin.adams{at}uni-duesseldorf.de),
    10. Martin Stangel, MD (stangel.martin{at}mh-hannover.de),
    11. Mike P. Wattjes, MD (wattjes.mike{at}mh-hannover.de),
    12. Günter Höglinger, MD (hoeglinger.guenter{at}mh-hannover.de) and
    13. Thomas Skripuletz, MD (skripuletz.thomas{at}mh-hannover.de)
  1. Franziska Hopfner, MD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. German Research Council (DFG), EASI-Genomics Consortium (Horizon 2020)

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Erwin-Röver-Foundation, Else-Kröner-Fresenius Foundation, CurePSP

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Nora Möhn, MD (moehn.nora{at}mh-hannover.de),
    3. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Speaker honoraria from Novartis and Merck

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Britta Eiz-Vesper, PhD (eiz-vesper.britta{at}mh-hannover.de),
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Britta Maecker-Kolhoff, MD (maecker.britta{at}mh-hannover.de),
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. BMBF_German Center for Infection Research

    Research Support, Academic Entities:

    1. German Research Foundation- SFB900_Project_B11

    Research Support, Foundations and Societies:

    1. Deutsche Kinderkrebsstiftung Deutsche Krebshilfe

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Jens Gottlieb, MD (gottlieb.jens{at}mh-hannover.de),
    6. Scientific Advisory Boards:

    1. ALTARA, THERAVANCE, MSD, ZAMBON, SPRINGER HEALTH CARE ALL COMMERCIAL, PAID TO ME

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NOVARTIS, BOEHRINGER BOTH COMMERCIAL

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. ZAMBON - COMMERCIAL FUNDING PAID TO INSTITUTION

    Research Support, Government Entities:

    1. DEUTSCHE FORSCHUNGSGEMEINSCHAFT, GERMAN CENTER FOR LUNG RESEARCH, BOTH NON-PROFIT, FUNDING PAID TO INSTITUTION

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. PFIZER - COMMERCIAL

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Rainer Blasczyk, MD (blasczyk.rainer{at}mh-hannover.de),
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. (1) Method for identifying T cell-stimulating protein fragments (2) Method for antigen-specific stimulation of T lymphocytes

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. German Red Cross

    Research Support, Government Entities:

    1. (1) German Federal Ministry of Health, ZMVI1-2520COR804, Principal Investigator, 2020-2021 (2) EU (ERDF) and German state of Lower Saxony, ZW 6-85019222, Principal Investigator, 2018-2022

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. Imusyn GmbH & Co. KG, 2019, 2020, 2021 Stock/Stock Options, Medical Equipment & Materials: Imusyn GmbH & Co. KG, 2019, 2020, 2021

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Nima Mahmoudi, MD (mahmoudi.nima{at}mh-hannover.de),
    8. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. Kaweh Pars, MD (kaweh.pars{at}uni-oldenburg.de),
    9. Scientific Advisory Boards:

    1. (1) Novartis, (2) Biogen, (3) Roche, (4) Sanofi-Aventis

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Frontiers in Neurology

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Roche

    Speakers' Bureaus:

    1. (1) Novartis

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Ortwin Adams, MD, PhD (ortwin.adams{at}uni-duesseldorf.de),
    10. Scientific Advisory Boards:

    1. On April 11th 2013 I participated on a expert meeting of Biogen Idec in Munich about the topic "Risk stratification for developing PML of MS patients with Natalizumab. I was not involved in any strategic or other decisions of Biogen Idec. I got a honorarium for participating.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Martin Stangel, MD (stangel.martin{at}mh-hannover.de),
    11. Scientific Advisory Boards:

    1. Alexion, Biogen, Bayer Healthcare, Takeda, Celgene, CSL Behring, Grifols, Janssen, Merck- Serono, Novartis, Roche, Sanofi-Aventis

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Travel and speaker honoraria from Bayer Healthcare, Biogen, CSL Behring, Merck-Serono, Novartis, Roche, Sanofi-Genzyme, and Teva

    Editorial Boards:

    1. PLoS ONE, Academic Editor; Multiple Sclerosis International, Editorial Board Member

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Biogen, Merck-Serono, Novartis, Sanofi-Aventis

    Research Support, Government Entities:

    1. Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), EU FP7

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Volkswagenstiftung

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Mike P. Wattjes, MD (wattjes.mike{at}mh-hannover.de),
    12. Scientific Advisory Boards:

    1. Biogen, Roche, IXICO, Novartis, Icometrix, Imcyse

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Biogen, BIOLOGIX, Novartis, Sanofi-Genzyme, Roche, Merck-Serono, Biologix, Springer Healthcare, Celgene, Bayer, MedDay, Genilac, Medison,

    Editorial Boards:

    1. European Radiology, 4 years, Editorial Board Member Neuroradiology, 2 years, Editorial Board Member Jounral of Neuroimaging, 2 years, Editorial Board Member

    Patents:

    1. NONE

    Publishing Royalties:

    1. "Neuromuscular Imaging" 2013, Springer Healthcare, "Diagnostik und Therapie neurologischer Erkrankungen State of the Art" Elsevier, 2019 and 2020

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Biogen, Roche, IXICO, Icometrix, Imcyse

    Speakers' Bureaus:

    1. Speaker honoraria: Biogen, BIOLOGIX, Novartis, Sanofi-Genzyme, Roche, Merck-Serono, Biologix, Springer Healthcare, Celgene, Bayer, MedDay, Genilac, Medison,

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Günter Höglinger, MD (hoeglinger.guenter{at}mh-hannover.de) and
    13. Scientific Advisory Boards:

    1. (1) Abbvie, (2) Alzprotect, (3) Asceneuron, (4) Bial, (5) Biogen, (6) Biohaven, (7) Lundbeck, (8) Novartis, (9) Roche, (10) Sanofi, (11) UCB

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1) Abbvie, (2) Alzprotect, (3) Asceneuron, (4) Bial, (5) Biogen, (6) Biohaven, (7) Lundbeck, (8) Novartis, (9) Roche, (10) Sanofi, (11) UCB

    Editorial Boards:

    1. Parkinsonism Related Disorders, Neurogenetics

    Patents:

    1. NONE

    Publishing Royalties:

    1. (1) Stamelou M, Hoglinger GU (Ed.). Parkinsonism Beyond Parkinson?s Disease, International Review of Neurobiology, London, 2019. (2) Hoglinger GU (Ed.). Parkinson Syndrome kompakt, Thieme, Stuttgart, 2018.

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Abbvie, (2) Alzprotect, (3) Asceneuron, (4) Bial, (5) Biogen, (6) Biohaven, (7) Lundbeck, (8) Novartis, (9) Roche, (10) Sanofi, (11) UCB

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Abbvie, (2) Biogen, (3) Biohaven, (4) Novartis, (5) Sanofi, (6) UCB

    Research Support, Government Entities:

    1. (1) Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany?s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy ? ID 390857198; HO2402/6-2 Heisenberg Program, HO2402/18-1 MSAomics), (2) German Federal Ministry of Education and Research (BMBF, 01KU1403A EpiPD; 01EK1605A HitTau), (3) EU/EFPIA/Innovative Medicines Initiative [2] Joint Undertaking (IMPRIND grant no 116060)(3) Lower Saxony Ministry for Science (Niedersachsisches Vorab)

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  13. Thomas Skripuletz, MD (skripuletz.thomas{at}mh-hannover.de)
    14. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Speaker honoraria: Alexion, Alnylam, Bayer Vital, Biogen, Celgene, Centogene, CSL Behring, Euroimmun, Merck, Novartis, Roche, Sanofi Aventis, Siemens. All outside the submitted work.

    Editorial Boards:

    1. 2018-2020 Frontiers in Neurology and Frontiers in Immunology (Guest Editor), Research Topic “New Cerebrospinal Fluid Research to Uncover Mechanisms Driving Neurological and Psychiatric Diseases” Since 2020 Cells (Guest Editor), Research Topic “Novel Insights on Cerebrospinal Fluid Research” Since 2020 Annals of Translational Medicine (Editorial Board)

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Department of Neurology (F.H., N. Möhn, M.S., G.H., T.S.), Hannover Medical School; Institute of Transfusion Medicine and Transplant Engineering (B.E.-V., R.B.), Hannover Medical School; Department of Pediatric Hematology and Oncology (B.M.-K.), Hannover Medical School; Hannover Medical School (B.M.-K.), Institute for Transfusion Medicine; Department of Respiratory Medicine (J.G.), Hannover Medical School; Department of Diagnostic and Interventional Neuroradiology (N. Mahmoudi, M.P.W.), Hannover Medical School, Hannover; Department of Neurology (N. Mahmoudi, K.P., M.P.W.), Carl Von Ossietzky University, Oldenburg; and Institute of Virology (O.A.), Medical Faculty, Heinrich-Heine University Düsseldorf, Germany.
  1. Correspondence
    Dr. Hopfner Hopfner.Franziska{at}mh-hannover.de
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