Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia
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...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Advances in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2012/595060 |
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| author | Philipp Koehler Patrick Schmidt Andreas A. Hombach Michael Hallek Hinrich Abken |
| author_facet | Philipp Koehler Patrick Schmidt Andreas A. Hombach Michael Hallek Hinrich Abken |
| author_sort | Philipp Koehler |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9a8bbaa09d9b4164b6b809e2604b4e15 |
| institution | Kabale University |
| issn | 1687-9104 1687-9112 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Hematology |
| spelling | doaj-art-9a8bbaa09d9b4164b6b809e2604b4e152025-02-03T05:52:51ZengWileyAdvances in Hematology1687-91041687-91122012-01-01201210.1155/2012/595060595060Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic LeukaemiaPhilipp Koehler0Patrick Schmidt1Andreas A. Hombach2Michael Hallek3Hinrich Abken4Department I of Internal Medicine, and Center for Molecular Medicine Cologne, University Hospital Cologne, Robert-Koch-Strasse 21, 50931 Cologne, GermanyDepartment I of Internal Medicine, and Center for Molecular Medicine Cologne, University Hospital Cologne, Robert-Koch-Strasse 21, 50931 Cologne, GermanyDepartment I of Internal Medicine, and Center for Molecular Medicine Cologne, University Hospital Cologne, Robert-Koch-Strasse 21, 50931 Cologne, GermanyDepartment I of Internal Medicine, and Center for Molecular Medicine Cologne, University Hospital Cologne, Robert-Koch-Strasse 21, 50931 Cologne, GermanyDepartment I of Internal Medicine, and Center for Molecular Medicine Cologne, University Hospital Cologne, Robert-Koch-Strasse 21, 50931 Cologne, GermanyB-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.http://dx.doi.org/10.1155/2012/595060 |
| spellingShingle | Philipp Koehler Patrick Schmidt Andreas A. Hombach Michael Hallek Hinrich Abken Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia Advances in Hematology |
| title | Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia |
| title_full | Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia |
| title_fullStr | Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia |
| title_full_unstemmed | Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia |
| title_short | Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia |
| title_sort | engineered t cells for the adoptive therapy of b cell chronic lymphocytic leukaemia |
| url | http://dx.doi.org/10.1155/2012/595060 |
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