CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:New insights into CAR T-cell hematological toxicities: manifestations, mechanisms, and effective management strategies.
New insights into CAR T-cell hematological toxicities: manifestations, mechanisms, and effective management strategies.
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嵌合抗原受体(CAR)T细胞疗法是一种高效治疗方式,已证明可改善恶性肿瘤患者结局,尤其是复发/难治性血液系统恶性肿瘤患者。然而,CAR-T 细胞疗法应用不断增加,也暴露出多种危及生命的毒性,尤其包括细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)、感染及血液学毒性(HT),从而阻碍了该疗法的广泛应用。HT涵盖多种不良反应,包括血细胞减少、噬血细胞性淋巴组织细胞增多症(HLH)、凝血障碍和B细胞缺如。尽管我们对CRS和ICANS潜在机制的认识不断加深,HT复杂的病理生理机制仍未得到充分阐明。知识缺口可能导致治疗决策不理想,进而造成大量医疗资源耗费并损害患者生活质量。本综述基于近期更新的研究结果,阐述CAR-T 细胞治疗后HT的各种机制、临床表现,并提出缓解这一重要临床挑战的策略。
Chimeric antigen receptor (CAR) T-cell therapy represents a highly efficacious treatment modality demonstrated to enhance outcomes in patients afflicted with malignancies, particularly those enduring relapsed or refractory hematological malignancies.
However, the escalating adoption of CAR T-cell therapy has unveiled several life-threatening toxicities, notably cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and hematological toxicities (HTs), thereby hindering the broad implementation of CAR T-cell therapy. HTs encompass a spectrum of adverse effects, including cytopenias, hemophagocytic lymphohistiocytosis (HLH), coagulopathies, and B-cell aplasia.
While our comprehension of the underlying mechanisms governing CRS and ICANS is advancing, the intricate pathophysiology of HTs remains inadequately elucidated. Such knowledge gaps may precipitate suboptimal therapeutic decisions, potentially culminating in substantial medical resource depletion and detriment to patients' quality of life.
In this comprehensive review, based on recent updated findings, we delineate various mechanisms contributing to HTs subsequent to CAR T-cell therapy, explicate manifestations of HTs, and proffer strategic interventions to mitigate this relevant clinical challenge.
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