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  • Original Article
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Graft-versus-Tumor Effects

Clinical-scale single-step CD4+ and CD8+ cell depletion for donor innate lymphocyte infusion (DILI)

Bone Marrow Transplantation volume 41, pages 643–650 (2008)Cite this article

Abstract

The ability to selectively deplete or enrich cells of specific phenotype by immunomagnetic selection to reduce the risk of GVHD holds significant promise for application in adoptive immunotherapy. Current clinical-scale approaches for T-cell depletion (e.g., CD34+ selection, CD3+ depletion), usually deplete γδ T cells, which may be advantageous in mediating graft-versus-tumor (GVT) effects and augmenting the innate immune response against infections. Here, we present a new method for depletion of T cells with potential GVHD reactivity by using a single-step immunomagnetic protocol, which efficiently depletes CD4+ and CD8+ αβ T cells under good manufacturing practice (GMP) conditions. Depletion from unstimulated leukapheresis products (n=6) containing up to 2.0 × 1010 cells showed high efficiency (mean log depletion of CD4+ cells: 4.12, CD8+ cells: 3.77). In addition, immunomagnetic CD4/CD8 depletion resulted in passive enrichment of innate lymphocytes (mean recovery of natural killer (NK) cells: 38%, γδ T cells: 50%). We demonstrated that γδ/NK cells preserved their proliferative and cytotoxic capacity and conclude that simultaneous large-scale depletion of CD4+/CD8+ T cells is feasible and can be performed under GMP conditions with high-depletion efficacy for αβ T cells and recovery of functionally intact innate effector lymphocytes for potential use in adoptive immunotherapy studies.

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Acknowledgements

We thank Rosemarie Ottohal, Martina Seubert, Heidi Heimlich, Elisabeth Holzmann, Manuela Stuewe and Hildegard Wessel for their expert technical assistance. This work was supported by Interdisziplinaeres Zentrum fuer Klinische Forschung Wuerzburg (IZKF, Grant no. 01KS9603) and Deutsche Forschungsgemeinschaft (DFG, Grant no. KFO 124/1-1 TP5). This work was presented in part at the ASH Meeting 2006.

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  1. Institute of Medical Oncology and Hematology, Klinikum Nürnberg, Nürnberg, Germany

    M Smetak, J Birkmann, K Schaefer-Eckart & M Wilhelm

  2. Medizinische Klinik und Poliklinik II Würzburg, University of Würzburg, Würzburg, Germany

    B Kimmel, H Einsele & V Kunzmann

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  1. M Smetak
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Correspondence to M Smetak.

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Smetak, M., Kimmel, B., Birkmann, J. et al. Clinical-scale single-step CD4+ and CD8+ cell depletion for donor innate lymphocyte infusion (DILI). Bone Marrow Transplant 41, 643–650 (2008). https://doi.org/10.1038/sj.bmt.1705942

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