A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells

Martin A. Pulè, Karin C. Straathof, Gianpietro Dotti, Helen Heslop, Cliona M. Rooney, Malcolm Brenner

Research output: Contribution to journalArticlepeer-review

347 Scopus citations

Abstract

The transduction of primary T cells to express chimeric T cell receptors (cTCR) for redirected targeting of tumor cells is an attractive strategy for generating tumor-specific T cells for adoptive therapy. However, tumor cells rarely provide costimulatory signals and hence cTCRs that transmit just a CD3ζ signal can only initiate target cell killing and interferon-γ release and fail to induce full activation. Although incorporation of a CD28 component results in IL-2 release and limited proliferation, T cell activation remains incomplete. OX40 transmits a potent and prolonged T cell activation signal and is crucial for maintaining an immunological response. We hypothesize that the CD28-OX40-CD3ζ tripartite cytoplasmic domain will provide a full complement of activation, proliferation, and survival signals for enhanced anti-tumor activity.

Original languageEnglish (US)
Pages (from-to)933-941
Number of pages9
JournalMolecular Therapy
Volume12
Issue number5
DOIs
StatePublished - Nov 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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