1. ¹Institute of Medical Oncology and Hematology, Klinikum Nürnberg, Nürnberg, Germany
2. ²Medizinische Klinik und Poliklinik II Würzburg, University of Würzburg, Würzburg, Germany

Correspondence: Dr M Smetak, Klinikum Nürnberg, Medizinische Klinik 5, Prof-Ernst-Nathan-Str. 1, Nürnberg D-90340, Germany. E-mail: smetak@klinikum-nuernberg.de

Received 8 August 2007; Revised 12 October 2007; Accepted 22 October 2007; Published online 26 November 2007.

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 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⁺ 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%, T cells: 50%). We demonstrated that /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 T cells and recovery of functionally intact innate effector lymphocytes for potential use in adoptive immunotherapy studies.