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- Title
632. Sustained Function and Enhanced Replicative Capacity of Anti-Tumor CD4+ Effectors by Enforced Co-Stimulation.
- Authors
Lufen Chang; Jensen, Michael
- Abstract
Optimal T-Cell activation for cytokine production, expansion and retention of effector functions requires multiple signals provided by co-stimulatory receptor signaling together with TCR-CD3 complex signaling. A chimeric antigen receptor (CAR) in our original redirected cytolytic T cells (CTLs) contains just a CD3z signal alone (Kahlon KS et al., 2004. Cancer Research), which may not be able to induce a full immune response in targeting tumors that rarely express costimulatory molecules. To circumvent this limitation, we improve the current CAR by addition of the cytoplasmic domain of CD28 and 4-1BB co-stimulator receptors. The resulting CAR composed of the CD28-41BB- CD3z tripartite cytoplasmic domain augments the levels of specific tumor-induced IL-2, INF-g gene expression and cytokine expression and accelerates cytolytic activity. Interestingly, combing z with CD28 and 41BB co-stimulation confers CD4+ effector cells on retention of immunological response to subsequent tumor antigen encounter in the absence of IL-2. Overall, this study has demonstrated that incorporation of costimulatory activity in CAR is a powerful approach to improve current immunotherapeutic strategies.Kahlon KS, Brown C, Cooper LJ, Raubitschek A, Forman SJ, Jensen MC.Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res. 2004 Dec 15;64(24):9160–166.Molecular Therapy (2006) 13, S243–S244; doi: 10.1016/j.ymthe.2006.08.707
- Subjects
CANCER; T cells; CELLULAR immunity; GENE expression; IMMUNE response; TUMORS
- Publication
Molecular Therapy, 2006, Vol 13, pS243
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2006.08.707