CAR-T in the Treatment of Acute Myeloid Leukemia: Barriers and How to Overcome Them

被引:16
作者
Vanhooren, Jolien [1 ,2 ,3 ]
Dobbelaere, Rani [1 ]
Derpoorter, Charlotte [1 ,2 ,3 ]
Deneweth, Larissa [2 ,3 ]
Van Camp, Laurens [1 ,2 ,3 ]
Uyttebroeck, Anne [4 ]
De Moerloose, Barbara [1 ,2 ,3 ]
Lammens, Tim [1 ,2 ,3 ]
机构
[1] Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium
[2] Ghent Univ Hosp, Dept Pediat Hematol Oncol & Stem Cell Transplantat, Ghent, Belgium
[3] Canc Res Inst Ghent, Ghent, Belgium
[4] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Pediat Hematol & Oncol, Dept Oncol, Leuven, Belgium
关键词
CHIMERIC ANTIGEN RECEPTOR; CELL IMMUNOTHERAPY; THERAPY; EXPRESSION; RELEASE; AML; IDENTIFICATION; CYTOTOXICITY; PROGNOSIS; BLASTS;
D O I
10.1097/HS9.0000000000000937
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Conventional therapies for acute myeloid leukemia (AML) are characterized by high rates of relapse, severe toxicities, and poor overall survival rates. Thus, the development of new therapeutic strategies is crucial for improving the survival and quality of life of AML patients. CD19-directed chimeric antigen receptor (CAR) T-cell immunotherapy has been extremely successful in the treatment of B-cell acute lymphoid leukemia and several mature B-cell lymphomas. However, the use of CAR T-cell therapy for AML is currently prevented due to the lack of a myeloid equivalent to CD19, as currently known cell surface targets on leukemic blasts are also expressed on healthy hematopoietic stem and progenitor cells as well as their progeny. In addition, the immunosuppressive tumor microenvironment has a dampening effect on the antitumor activity of CAR-T cells. Here, we review the therapeutic challenges limiting the use of CAR T-cell therapy for AML and discuss promising novel strategies to overcome them.
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页数:10
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