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Treatment of B cells malignancies with anti-CD19 CAR+, TCR-, CD52- allogeneic T cells
© Mannioui et al; licensee BioMed Central Ltd. 2013
Published: 7 November 2013
Encouraging data have emerged from adoptive T-cell therapies in advanced forms of cancer. Anti-tumor immunity is found in tumor infiltrating lymphocytes as well as engineered T cells where exogenous expression of a chimeric antigen receptor (CAR) confers cancer recognition on the cells. Present adoptive immunotherapy methods are restricted to the use of autologous patient T-cells due to the limited persistence of allogeneic T cells and the potential for graft versus host disease (GvHD). The use of autologous patient T cells in cancer immunotherapy is however limited due to the fact that this approach is complex and time consuming. We propose a novel approach to treat B cell malignancies based on the use of genetically modified allogeneic T cells in conjunction with the conditioning regimen alemtuzumab. Allogeneic T cells were engineered to express an anti-CD19 CAR and to no longer express TCRalpha and CD52, responsible for GVHD and the sensitivity to alemtuzumab, respectively. The inactivation of the TCRalpha and CD52 genes in allogeneic T cells was realized by using TALENTM, a novel class of sequence-specific nucleases created by the fusion of transcription activator-like effectors (TALEs) to the catalytic domain of an endonuclease. We have shown that anti-CD19 CAR+ TCR- CD52- allogeneic T cells did not respond to TCR stimulation, were resistant to alemtuzumab treatment and were able to kill target cells expressing CD19 in vitro and in vivo.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.