Facilitating matched pairing and expression of TCR chains introduced into human T cells

Jürgen Kuball, Michelle L. Dossett, Matthias Wolfl, William Y. Ho, Ralf Holger Voss, Carla Fowler, Philip D. Greenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Adoptive transfer of T lymphocytes is a promising treatment for a variety of malignancies but often not feasible due to difficulties generating T cells that are reactive with the targeted antigen from patients. To facilitate rapid generation of cells for therapy, T cells can be programmed with genes encoding the α and β chains of an antigen-specific T-cell receptor (TCR). However, such exogenous α and β chains can potentially assemble as pairs not only with each other but also with endogenous TCR α and β chains, thereby generating αβTCR pairs of unknown specificity as well as reducing the number of exogenous matched αβTCR pairs at the cell surface. We demonstrate that introducing cysteines into the constant region of the α and β chains can promote preferential pairing with each other, increase total surface expression of the introduced TCR chains, and reduce mismatching with endogenous TCR chains. This approach should improve both the efficacy and safety of ongoing efforts to use TCR transfer as a strategy to generate tumor-reactive T cells.

Original languageEnglish (US)
Pages (from-to)2331-2338
Number of pages8
JournalBlood
Volume109
Issue number6
DOIs
StatePublished - Mar 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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