Cytokine Release Syndrome Associated with T-Cell-Based Therapies for Hematological Malignancies: Pathophysiology, Clinical Presentation, and Treatment

被引:64
|
作者
Cosenza, Maria [1 ]
Sacchi, Stefano [1 ]
Pozzi, Samantha [1 ]
机构
[1] Univ Modena & Reggio Emilia, Dept Med & Surg Sci, I-41124 Modena, Italy
关键词
cytokine release syndrome; CAR T cell therapy; monoclonal antibodies; hematological malignancies; C-REACTIVE PROTEIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; FACTOR GM-CSF; B-CELL; MACROPHAGE ACTIVATION; JAK-STAT; INFLAMMATION; GAMMA; IL-6; INTERLEUKIN-6;
D O I
10.3390/ijms22147652
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cytokines are a broad group of small regulatory proteins with many biological functions involved in regulating the hematopoietic and immune systems. However, in pathological conditions, hyperactivation of the cytokine network constitutes the fundamental event in cytokine release syndrome (CRS). During the last few decades, the development of therapeutic monoclonal antibodies and T-cell therapies has rapidly evolved, and CRS can be a serious adverse event related to these treatments. CRS is a set of toxic adverse events that can be observed during infection or following the administration of antibodies for therapeutic purposes and, more recently, during T-cell-engaging therapies. CRS is triggered by on-target effects induced by binding of chimeric antigen receptor (CAR) T cells or bispecific antibody to its antigen and by subsequent activation of bystander immune and non-immune cells. CRS is associated with high circulating concentrations of several pro-inflammatory cytokines, including interleukins, interferons, tumor necrosis factors, colony-stimulating factors, and transforming growth factors. Recently, considerable developments have been achieved with regard to preventing and controlling CRS, but it remains an unmet clinical need. This review comprehensively summarizes the pathophysiology, clinical presentation, and treatment of CRS caused by T-cell-engaging therapies utilized in the treatment of hematological malignancies.
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页数:14
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