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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Overview of infectious complications among CAR T- cell therapy recipients.
Overview of infectious complications among CAR T- cell therapy recipients.
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CAR-T 已改变血液恶性肿瘤治疗,但可引起CRS、免疫效应细胞相关神经毒性、血液毒性及机会性感染等不良事件。不同CAR靶点对应不同感染流行病学和危险因素,也会因靶向肿瘤外效应不同而导致不同的长期免疫缺陷;用于管理CRS和神经毒性的多模式免疫抑制又会加重风险。感染管理的关键包括制定筛查、预防和监测方案,并明确免疫球蛋白替代及重新接种疫苗的作用,同时考虑既往免疫调节治疗、基础恶性肿瘤、CAR靶点以及相关不良事件的发生和管理。本文指出,CAR-T 感染管理认识正不断加深;随着更多效应细胞和CAR靶点出现,策略仍将持续演进。
Chimeric antigen receptor-modified T cell (CAR T-cell) therapy has revolutionized the management of hematological malignancies.
In addition to impressive malignancy-related outcomes, CAR T-cell therapy has significant toxicity-related adverse events, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), immune effector cell-associated hematotoxicity (ICAHT), and opportunistic infections. Different CAR T-cell targets have different epidemiology and risk factors for infection, and these targets result in different long-term immunodeficiency states due to their distinct on-target and off- tumor effects.
These effects are exacerbated by the use of multimodal immunosuppression in the management of CRS and ICANS. The most effective course of action for managing infectious complications involves determining screening, prophylactic, and monitoring strategies and understanding the role of immunoglobulin replacement and re-vaccination strategies. This involves considering the nature of prior immunomodulating therapies, underlying malignancy, the CAR T-cell target, and the development and management of related adverse events.
In conclusion, we now have an increasing understanding of infection management for CAR T-cell recipients. As additional effector cells and CAR T-cell targets become available, infection management strategies will continue to evolve.
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