Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia.pdfVIP

Hindawi Publishing Corporation Advances in Hematology Volume 2012, Article ID 595060, 13 pages doi:10.1155/2012/595060 Review Article Engineered T Cells for the Adoptive Therapy of B-Cell Chronic Lymphocytic Leukaemia Philipp Koehler, Patrick Schmidt, Andreas A. Hombach, Michael Hallek, and Hinrich Abken Department I of Internal Medicine, and Center for Molecular Medicine Cologne, University Hospital Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany Correspondence should be addressed to Hinrich Abken, hinrich.abken@uk-koeln.de Received 22 February 2011; Revised 13 May 2011; Accepted 23 May 2011 Academic Editor: Cheng-Kui Qu Copyright © 2012 Philipp Koehler et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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,