Clinical Immunotherapy of B-Cell Malignancy Using CD19-Targeted CAR T-Cells
CAR Mechanics Group, King's College London, King's Health Partners Integrated Cancer Centre, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, UK.
AbstractThe CD19 molecule is ubiquitously expressed throughout all stages of B-cell differentiation, but is not found on haemopoietic stem cells. Since most B-cell leukaemias and lymphomas retain CD19 expression, it represents an excellent target for immunotherapy of these malignant disorders. Over the past 10 years, compelling pre-clinical evidence has accrued to indicate that expression of a CD19-targeted chimeric antigen receptor (CAR) in peripheral blood T-cells exerts therapeutic efficacy in diverse models of B-cell malignancy. Building on this, clinical studies are ongoing in several centres in which autologous CD19-specific CAR T-cells are undergoing evaluation in patients with acute and chronic B-cell leukaemia and refractory lymphoma. Early data have generated considerable excitement, providing grounds to speculate that CAR-based immunotherapy will radically alter existing management paradigms in B-cell malignancy. The focus of this mini-review is to evaluate these emerging clinical data and to speculate on clinical prospects for this new therapeutic modality.
Adoptive immunotherapy, CD19, chimeric antigen receptor, gene therapy, leukaemia, lymphoma.
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