1. Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia.
- Author
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Koehler, Philipp, Schmidt, Patrick, Hombach, Andreas A., Hallek, Michael, and Abken, Hinrich
- Subjects
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T cells , *CHRONIC lymphocytic leukemia , *B cells , *CANCER relapse , *CLINICAL trials , *CHIMERIC proteins , *ANTIGEN receptors , *MAJOR histocompatibility complex , *CD19 antigen - Abstract
B-cell chronic lymphocytic leukaemia (B-CLL) remains an incurable disease due to the high risk of relapse, even after complete remission, raising the need to control and eliminate residual tumor cells in long term. Adoptive T cell therapy with genetically engineered specificity is thought to fulfil expectations, and clinical trials for the treatment of CLL are initiated. Cytolytic T cells from patients are redirected towards CLL cells by ex vivo engineering with a chimeric antigen receptor (CAR) which binds to CD19 on CLL cells through an antibody-derived domain and triggers T cell activation through CD3ζ upon tumor cell engagement. Redirected T cells thereby target CLL cells in an MHC-unrestricted fashion, secret proinflammatory cytokines, and eliminate CD19+ leukaemia cells with high efficiency. Cytolysis of autologous CLL cells by patient's engineered T cells is effective, however, accompanied by lasting elimination of healthy CD19+ B-cells. In this paper we discuss the potential of the strategy in the treatment of CLL, the currently ongoing trials, and the future challenges in the adoptive therapy with CAR-engineered T cells. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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