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Gene Transfer of MHC-Restricted Receptors

  • Helmut W. H. G. Kessels
  • Monika C. Wolkers
  • Ton N. M. Schumacher
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 109)

Abstract

Adoptive therapy with allogeneic or tumor-specific T-cells has shown substantial clinical effects for several human tumors, but the widespread application of this strategy remains a daunting task. The antigen specificity of T-lymphocytes is solely determined by the T-cell receptor (TCR) α and β chains. Consequently, genetic transfer of TCR chains may form an alternative and potentially appealing strategy to impose a desirable tumor-antigen specificity onto cytotoxic or helper T-cell populations. In this strategy, autologous or donor-derived T-cell populations are equipped with a TCR of defined reactivity in short-term ex vivo cultures, and re-infusion of the redirected cells is used to supply T-cell reactivity against defined tumor-specific antigens. We have previously described the genetic introduction of T-cell receptor genes into peripheral T-cells in mouse model systems. Here we discuss the requirements for the successful genetic modification of murine T-lymphocytes and the subsequent use of such genetically modified cells in in vivo models.

Key Words

T-cell receptor gene therapy adoptive transfer immunotherapy retroviral vectors 

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Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Helmut W. H. G. Kessels
    • 1
  • Monika C. Wolkers
    • 1
  • Ton N. M. Schumacher
    • 1
  1. 1.Department of ImmunologyThe Netherlands Cancer InstituteAmsterdamThe Netherlands

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