Sunderland, MW;
Peggs, KS;
(2018)
Successful translation and future prospects of TALEN editing for leukemia patients.
Expert Opinion on Biological Therapy
, 18
(7)
pp. 725-726.
10.1080/14712598.2018.1484105.
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Abstract
n recent years chimeric antigen receptor (CAR) T cell therapies have emerged as powerful targeted immunotherapies [1]. They have had impressive success in the treatment of different types of B cell leukemias, with early phase trials of CAR T cell therapy against the B cell antigen CD19 (CAR19) accomplishing disease remission in a significant proportion of treated patients [2]. The process for the generation of these autologous CAR T cells requires leukapheresis for the isolation of the T cells, followed by genetic engineering to express the desired CAR against one or more B cell antigens (e.g. CD19, CD22) on their surface. Finally, these CAR T cells are expanded and, after the patient has been lymphodepleted using combination chemotherapy, they are reinfused. Because these are patient-specific therapies, the manufacturing of these cells has proven to be expensive, time-consuming, and in some cases technically difficult, especially in patients that have been extensively treated and rendered lymphopenic. Due to these difficulties, there has been marked interest in generating an ‘off-the-shelf’, universal CAR T cell that could be derived from unrelated donors. There are two major barriers in this regard. The first involves the recognition of the patient’s human leucocyte antigens (HLA) by the native T cell receptor (TCR) of the CAR T cells, potentially causing transfusional graft-versus-host disease (GvHD), which often manifests with cytopenias and is potentially life threatening. The second involves the foreign HLA expressed by the CAR T cells being recognized by the immune system of the patient (hence rejection of the CAR T cells).
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