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- Title
A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells
- Authors
Pulè, Martin A.; Straathof, Karin C.; Dotti, Gianpietro; Heslop, Helen E.; Rooney, Cliona M.; Brenner, Malcolm K.
- Abstract
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.
- Subjects
LYMPHOCYTES; CANCER cells; T cell receptors; ANTINEOPLASTIC agents
- Publication
Molecular Therapy, 2005, Vol 12, Issue 5, p933
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2005.04.016