Journal
MOLECULAR THERAPY
Volume 12, Issue 5, Pages 933-941Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2005.04.016
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Funding
- NCI NIH HHS [P01 CA94237, P01 CA094237-03, P01 CA094237] Funding Source: Medline
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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 CD3 zeta signal can only initiate target cell killing and interferon-gamma 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-CD3 zeta tripartite cytoplasmic domain will provide a full complement of activation, proliferation, and survival signals for enhanced anti-tumor activity.
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