Selective Expansion of Genetically Modified T Cells Using a Chimeric IL-2 Receptor for Cancer Therapy

  • Takahiro Sogo
  • Masahiro Kawahara
  • Hiroshi Ueda
  • Teruyuki Nagamune
Conference paper
Part of the Animal Cell Technology: Basic & Applied Aspects book series (ANICELLTECH, volume 15)

Abstract

T cells have been used for cancer immunotherapy because they play a central role in the cellular immunity. One approach to cure cancers is that tumor-specific T cells are activated in vitro and subsequently injected into patients. However, desired therapeutic effect has not been attained due to difficulty to ­maintain activated T cells for a prolonged period after injection. To solve this problem, we thought to use an interleukin (IL)-2-dependent growth signal in T cells for maintenance of activated T cells. If non-toxic molecules can substitute for the function of IL-2, genetically modified T cells can be expanded selectively without IL-2 and no side effect would occur. In this study, we replaced IL-2 binding domains of IL-2 receptor (IL-2R) β and γ chains by antibody variable regions recognizing a cognate antigen. Because these chimeric IL-2Rs could replace an IL-2-mediated signal by an antigen-mediated one, only the T cells with these chimeric receptors would grow in the presence of the cognate antigen but without IL-2.

Keywords

T cell IL-2 IL-2 receptor antibody variable region chimeric receptor 

References

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    Brielmeier M. et al, Improving stable transfection efficiency: antioxidants dramatically improve the outgrowth of clones under dominant marker selection. Nucleic Acids Res., 26, 2082–2085 (1998).CrossRefPubMedGoogle Scholar
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    Kawahara M. et al, Selection of genetically modified cell population using hapten-specific antibody/receptor chimera. Biochem. Biophys. Res. Commun., 315, 132–138 (2004).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Takahiro Sogo
    • 1
  • Masahiro Kawahara
    • 1
  • Hiroshi Ueda
    • 1
  • Teruyuki Nagamune
    • 1
  1. 1.Department of Chemistry and Biotechnology, Graduate School of EngineeringThe University of TokyoTokyoJapan

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