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T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30+ cutaneous lymphoma cells

Gene Therapy volume 8, pages 891–895 (2001)Cite this article

Abstract

T cells can be directed to antigen-specific, MHC-independent target cell lysis by grafting with a recombinant receptor with antibody-like specificity. Here, we asked whether T cells from the peripheral blood of a patient with cutaneous T cell lymphoma can be recruited for an immune response against autologous tumor cells. Lymphoma cells with a CD3− CD4+ CD30+ phenotype and clonal TCR-Vβ7 rearrangement were isolated from a cutaneous lesion. The lymphoma lesion additionally harbored CD3+ CD25+ activated normal T cells despite ongoing tumor progression. Peripheral blood-derived T cells from the lymphoma patient were retrovirally engrafted with a recombinant anti-CD30-scFv-γ receptor. Upon cocultivation with autologous CD30+lymphoma cells, grafted T cells increase IFN-γ secretion and lyse specifically lymphoma cells with high efficiency, even at an effector to target cell ratio of as low as 1:20. Our data demonstrate that the recombinant anti-CD30-γ receptor overcomes T cell tolerance for tumor cells and directs T cells specifically against autologous lymphoma cells.

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Acknowledgements

We would like to thank Dr RL Bolhuis (Department of Clinical and Tumor Immunology, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands) for providing us with the retroviral expression vector pSTITCH. This work is supported by grants from the Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany, through SFB 502, the Deutsche Krebshilfe, Bonn, through 70–2235-Ab1 and 70–2091-Lu1, and the Köln Fortune Program.

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Authors and Affiliations

  1. Department I of Internal Medicine, Laboratory Tumor Genetics, University of Cologne, Germany

    A Hombach, M Gerken, C Heuser & H Abken

  2. St Elisabeth-Krankenhaus Köln-Hohenlind, Cologne, Germany

    J M Muche, S Gellrich & W Sterry

  3. Department of Dermatology and Allergy, University Hospital Charité, Humboldt University Berlin, Berlin, Germany

    C Pohl

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  1. A Hombach
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  2. J M Muche
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  3. M Gerken
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  4. S Gellrich
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  5. C Heuser
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  6. C Pohl
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  7. W Sterry
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  8. H Abken
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Hombach, A., Muche, J., Gerken, M. et al. T cells engrafted with a recombinant anti-CD30 receptor target autologous CD30+ cutaneous lymphoma cells. Gene Ther 8, 891–895 (2001). https://doi.org/10.1038/sj.gt.3301467

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