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The CD20/αCD20 ‘suicide’ system: novel vectors with improved safety and expression profiles and efficient elimination of CD20-transgenic T cells

Gene Therapy volume 13, pages 789–797 (2006)Cite this article

Abstract

Adoptive transfer of T lymphocytes is an attractive strategy for many experimental treatment strategies for cancer. Unfortunately, manipulated T cells could be responsible for serious adverse events. Retroviral CD20-transduced T cells may be able to control these unwanted effects. CD20-positive cells are sensitive to rituximab (RTX), a monoclonal antibody specific for CD20. This permits their selective elimination in vivo in case of adverse events. To this end, a system is required that permits efficient and safe transduction of donor T cells and effective elimination of CD20-positive T cells. We constructed different CD20-encoding retroviral vectors and investigated the impact of inclusion of the woodchuck post-transcriptional regulatory element (WPRE) and the chicken hypersensitivity site 4 insulator elements on the levels, homogeneity and stability of CD20 expression. Importantly, inclusion of either WPRE or insulator elements in the retroviral vector resulted in a dramatic improvement in the stability of CD20 expression. The insulator element also led to a much more homogeneous level of CD20 expression. We also show the efficient elimination of the CD20-transgenic T cells via RTX by different effector mechanisms. In conclusion, we have constructed CD20-encoding retroviral vectors with improved efficiency and safety profiles, which can be used as a suicide strategy.

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Acknowledgements

We are grateful to Dr Ton NM Schumacher (Netherlands Cancer Institute, Amsterdam, The Netherlands) for providing the pMX retroviral vector; Dr Gary Nolan (Stanford University, Stanford, CA) for the amphotrophic packaging cell line Phoenix; Dr Christopher Baum for the WPRE element and Dr Gary Felsenfeld for insulator elements. The work was supported by EC Grant QLK3 CT 2001-01265.

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Authors and Affiliations

  1. Department of Haematology, Jordan Laboratory for Hemato-Oncology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands

    T van Meerten, M-J Claessen, A Hagenbeek & S B Ebeling

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  1. T van Meerten
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Correspondence to S B Ebeling.

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van Meerten, T., Claessen, MJ., Hagenbeek, A. et al. The CD20/αCD20 ‘suicide’ system: novel vectors with improved safety and expression profiles and efficient elimination of CD20-transgenic T cells. Gene Ther 13, 789–797 (2006). https://doi.org/10.1038/sj.gt.3302705

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