The CD20/alphaCD20 'suicide' system: novel vectors with improved safety and expression profiles and efficient elimination of CD20-transgenic T cells

Gene Ther. 2006 May;13(9):789-97. doi: 10.1038/


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / adverse effects*
  • Adoptive Transfer / methods
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / genetics*
  • Cell Death
  • Clone Cells
  • Flow Cytometry
  • Gene Expression
  • Genes, Transgenic, Suicide*
  • Genetic Engineering
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / therapy*
  • Humans
  • Lymphocyte Depletion
  • Retroviridae / genetics
  • Rituximab
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Transduction, Genetic / methods


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Rituximab