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Ex vivo expansion of autologous, donor-derived NK-, γδT-, and cytokine induced killer (CIK) cells post haploidentical hematopoietic stem cell transplantation results in increased antitumor activity

Bone Marrow Transplantation volume 54, pages 727–732 (2019)Cite this article

Abstract

Posttransplant treatment strategies are narrowed by the vulnerability of bone marrow. Building on immune cells with antitumor activity is a growing field in cancer therapy. Thus, transfer of expanded and preactivated immune cells is a promising intensification of treatment in high-risk tumor patients. We tested ex vivo expanded NK-, γδT-, and CIK cells that were generated by coincubation with irradiated K562-mb15-41BBL and Il2 and compared the expansion conditions of PBMCs versus CD3-depleted PBMCs as well as static versus semi-automated expansion. The median fold expansion was significantly higher using PBMCs and static expansion conditions. Expanded cells were preactivated with a CD56brightCD69high immunophenotype exerting excellent direct cellular cytotoxicity as well as ADCC in various tumor entities. We established a large-scale clinical-grade ex vivo expansion and activation protocol of NK-, γδT-, and CIK cells from donor-derived PBMCs of patients after haploidentical HSCT. In a patient with AML, NK/γδT/CIK cell transfer was associated with MRD response. A significant increase of direct antitumor activity and ADCC post cell transfer was documented. The results that we report here provide the rationale for clinical testing of expanded, preactivated NK/γδT/CIK cells for cancer therapy.

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Acknowledgements

K562-mb15-41BBL was kindly provided by Dario Campana, Singapore.

Funding

The authors acknowledge financial support by the Deutsche Forschungsgemeinschaft (DFG), CRC685 Immunotherapy, the Bundesministerium für Bildung und Forschung (BMBF-iVac-ALL, BMBF-GO-Bio 0315096/0316070), the Reinhold Beitlich Stiftung, the Stefan Morsch Stiftung, the Förderverein für krebskranke Kinder Tübingen, the German Cancer Consortium (DKTK) and the German Cancer Research Center (DKFZ) Heidelberg, Germany. Publication of this supplement was sponsored by Gilead Sciences Europe Ltd, Cell Source, Inc., The Chorafas Institute for Scientific Exchange of the Weizmann Institute of Science, Kiadis Pharma, Miltenyi Biotec, Celgene, Centro Servizi Congressuali, Almog Diagnostic.

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Authors and Affiliations

  1. University Children’s Hospital, Department of Pediatric Hematology and Oncology, University of Tuebingen, Tuebingen, Germany

    Patrick Schlegel, Anne-Marie Lang, Marie Matela, Annika Horrer, Anne Schilling, Alexander Jöchner, Max Wiedenmann, Christian Seitz, Michaela Döring, Florian Heubach, Armin Rabsteyn, Rupert Handgretinger & Peter Lang

  2. Dr. von Hauner University Children’s Hospital, Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Munich, Germany

    Tobias Feuchtinger

  3. German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tübingen, Tuebingen, Germany

    Armin Rabsteyn

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  1. Patrick Schlegel
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Correspondence to Patrick Schlegel.

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Schlegel, P., Lang, AM., Matela, M. et al. Ex vivo expansion of autologous, donor-derived NK-, γδT-, and cytokine induced killer (CIK) cells post haploidentical hematopoietic stem cell transplantation results in increased antitumor activity. Bone Marrow Transplant 54 (Suppl 2), 727–732 (2019). https://doi.org/10.1038/s41409-019-0609-y

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