The treatment of relapsed or refractory leukemia remains a major challenge in pediatric and adult patients. A better understanding of the immune system in carcinogenesis has allowed the development of innovative treatment strategies. Immunotherapies using modified T-cells called chimeric antigen receptor (CAR) T-cells have shown very promising results initially in the treatment of melanoma and more recently in the treatment of acute lymphoblastic leukemia (ALL). CAR T-cells originate from the patient and are transfected in vitro by a lentiviral vector allowing them to express a chimeric receptor capable of recognizing tumor cells. This chimera combines variable domains of the heavy and light chains of an immunoglobutin specific for an epitope present on the tumor with the transmembrane and cytoplasmic portions of costimulatory proteins involved in the activation of T lymphocytes. Complete remission rates of up to 90% with durable responses have been reported using anti-CD19 CART-cells in the treatment of relapsed or refractory B-ALL. The management of toxicities related to cytokine release syndrome resulting from the activation of CAR T-cells is also a new challenge of this therapy. Many phases I/II clinical trials are ongoing in the world. In ALL, the use of CAR T-cells as a bridge to hematopoietic stem cells transplantation is also under evaluation. (C) 2016 Elsevier Masson SAS. All rights reserved.
机构:
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
German Canc Res Ctr, Targeted Tumor Vaccines Grp, Clin Cooperat Unit Appl Tumor Immun, Heidelberg, GermanyKarolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
Poorebrahim, Mansour
论文数: 引用数:
h-index:
机构:
Melief, Jeroen
Pico de Coana, Yago
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Oncol Pathol, Stockholm, SwedenKarolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
Pico de Coana, Yago
Wickstrom, Stina L.
论文数: 0引用数: 0
h-index: 0
机构:
Karolinska Inst, Dept Oncol Pathol, Stockholm, SwedenKarolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
Wickstrom, Stina L.
Cid-Arregui, Angel
论文数: 0引用数: 0
h-index: 0
机构:
German Canc Res Ctr, Targeted Tumor Vaccines Grp, Clin Cooperat Unit Appl Tumor Immun, Heidelberg, GermanyKarolinska Inst, Dept Oncol Pathol, Stockholm, Sweden