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Chronic Lymphocytic Leukemia

Redirection of CMV-specific CTL towards B-CLL via CD20-targeted HLA/CMV complexes

Leukemia volume 20, pages 1096–1102 (2006)Cite this article

Abstract

B-cell chronic lymphocytic leukaemia (B-CLL) is a slowly progressing malignancy of CD5+ B cells, for which at present no curative treatment is available. In our current study, we apply a novel bridging reagent to redirect cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) to target B-CLL. A streptavidin-fused anti-CD20 single-chain variable fragment (scFv) is used in combination with biotinylated MHC class I molecules containing CMV pp65 peptide (HLA/CMV). We demonstrate that B-CLL cells coated with this CD20-HLA/CMV complex can be lysed by autologous CMV-specific CTL with similar efficiency as B-CLL cells directly loaded with CMV peptide. Killing is HLA restricted and occurs at scFv CD20 concentrations of ⩾100 ng ml−1 and HLA/CMV concentrations of ⩾20 ng ml−1. Furthermore, complex-coated B-CLL cells induce both proliferation and cytokine production (interferon γ, tumour necrosis factor α and macrophage inflammatory protein−1 β) in CMV-specific CD8+ T cells. Hereby, a necessary step towards possible application of CD20-HLA/CMV complexes for immunotherapy of B-cell malignancies is constituted.

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Acknowledgements

We thank Berend Hooibrink for flowcytometric sorting of IFN-γ-secreting cells.

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Authors and Affiliations

  1. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands

    R Mous & M H J van Oers

  2. Alexis Biotech Ltd, London, UK

    P Savage

  3. Department of Medical Oncology, Charing Cross Hospital, London, UK

    P Savage

  4. Laboratory of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands

    E B M Remmerswaal, R A W van Lier & E Eldering

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  1. R Mous
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  2. P Savage
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  4. R A W van Lier
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  6. M H J van Oers
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Correspondence to R Mous.

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Mous, R., Savage, P., Remmerswaal, E. et al. Redirection of CMV-specific CTL towards B-CLL via CD20-targeted HLA/CMV complexes. Leukemia 20, 1096–1102 (2006). https://doi.org/10.1038/sj.leu.2404185

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