Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation

Authors

  • Monica Killig,

    1. Innate Immunity, Deutsches Rheuma Forschungszentrum, Berlin, Germany
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    • These authors contributed equally to this work.

  • Birte Friedrichs,

    1. Medical Clinic III, Haematology and Oncology, Charité Campus Benjamin Franklin, Berlin, Germany
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    • These authors contributed equally to this work.

  • Johannes Meisig,

    1. Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany
    2. Institute for Theoretical Biology, Humboldt Universität, Berlin, Germany
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  • Chiara Gentilini,

    1. Medical Clinic III, Haematology and Oncology, Charité Campus Benjamin Franklin, Berlin, Germany
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  • Nils Blüthgen,

    1. Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany
    2. Institute for Theoretical Biology, Humboldt Universität, Berlin, Germany
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  • Christoph Loddenkemper,

    1. Institute of Pathology, Charité Campus Benjamin Franklin, Berlin, Germany
    Current affiliation:
    1. Pathotres Joint Practice for Pathology, Berlin, Germany
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  • Myriam Labopin,

    1. ALWP, EBMT-Paris Office, Hôpital Saint Antoine, Service d'hématologie et thérapie cellulaire, AP-HP, UPMC Univ Paris 06, Paris, France
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  • Nadezda Basara,

    1. Medical Clinic II, Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany
    Current affiliation:
    1. Medizinischen Klinik I, Flensburg, Germany
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  • Christian Pfrepper,

    1. Medical Clinic II, Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany
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  • Dietger W. Niederwieser,

    1. Medical Clinic II, Department of Hematology, Oncology and Hemostaseology, University of Leipzig, Leipzig, Germany
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  • Lutz Uharek,

    1. Medical Clinic III, Haematology and Oncology, Charité Campus Benjamin Franklin, Berlin, Germany
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  • Chiara Romagnani

    Corresponding author
    1. Innate Immunity, Deutsches Rheuma Forschungszentrum, Berlin, Germany
    • Full correspondence Dr. Chiara Romagnani, Innate Immunity, Deutsches Rheuma Forschungszentrum, Charitéplatz 1, 10117 Berlin, Germany

      Fax: +49-3028460603

      e-mail: romagnani@drfz.de

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Abstract

Haploidentical stem cell transplantation (haploSCT) offers an alternative treatment option for advanced leukemia patients lacking a HLA-compatible donor. Transfer of NK cells represents a promising therapeutic option in combination with SCT, as NK cells can promote graft versus leukemia with low risk of GVH disease. In this study, we show results from a phase I/II trial in which 24 acute myeloid leukemia patients underwent haploSCT in combination with early transfer of unmodified NK cells and observed a promising 2-year overall survival rate of 37%. By performing immunomonitoring and subsequent principal component analysis, we tracked donor NK-cell dynamics in the patients and distinguished between NK cells reconstituting from CD34+ precursors, giving rise over time to a continuum of multiple differentiation stages, and adoptively transferred NK cells. Transferred NK cells displayed a mature phenotype and proliferated in vivo during the early days after haploSCT even in the absence of exogenous IL-2 administration. Moreover, we identified the NK-cell phenotype associated with in vivo expansion. Thus, our study indicates a promising path for adoptive transfer of unmodified NK cells in the treatment of high-risk acute myeloid leukemia.

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