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:Severe infections in recipients of cancer immunotherapy: what intensivists need to know.
Severe infections in recipients of cancer immunotherapy: what intensivists need to know.
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鉴于ICU收治的癌症患者数量增加,以及免疫治疗在其治疗方案中日益重要的地位,重症医学科医生将越来越多地面对接受免疫治疗并出现并发症(感染性和免疫性)的患者。
除了其特定的免疫毒性外,癌症免疫治疗接受者还存在特定的免疫功能障碍,并面临增加的感染风险,可能导致重症监护室入院。总结:CAR-T 细胞治疗与深度免疫抑制相关,细菌、真菌和病毒感染的风险根据输注后的时间而变化。免疫检查点阻断剂总体上具有有利的安全性特征,但检查点阻断剂与用于治疗免疫相关不良事件的皮质类固醇和免疫抑制药物的联合使用与细菌和真菌感染风险增加相关。T细胞衔接双特异性疗法blinatumomab导致深度B细胞发育不全、低丙种球蛋白血症和中性粒细胞减少症,但与标准强化化疗相比,似乎与较少的感染性不良事件相关。最后,膀胱内注射卡介苗(BCG)可导致播散性BCG炎和严重脓毒症,需要特定的抗生素治疗,通常与皮质类固醇治疗相关。
PURPOSE OF REVIEW: Given the increased number of cancer patients admitted in the ICU and the growing importance of immunotherapy in their therapeutic arsenal, intensivists will be increasingly confronted to patients treated with immunotherapies who will present with complications, infectious and immunologic. RECENT FINDINGS: Apart from their specific immunologic toxicities, cancer immunotherapy recipients also have specific immune dysfunction and face increased infectious risks that may lead to intensive care unit admission. SUMMARY: Chimeric antigen receptor T-cell therapy is associated with profound immunosuppression and the risks of bacterial, fungal and viral infections vary according to the time since infusion.
Immune checkpoint blockers are associated with an overall favorable safety profile but associations of checkpoint blockers and corticosteroids and immunosuppressive drugs prescribed to treat immune-related adverse events are associated with increased risks of bacterial and fungal infections.
The T-cell engaging bispecific therapy blinatumomab causes profound B-cell aplasia, hypogammaglobulinemia and neutropenia, but seems to be associated with fewer infectious adverse events compared with standard intensive chemotherapy. Lastly, intravesical administration of Bacillus Calmette-Guérin (BCG) can lead to disseminated BCGitis and severe sepsis requiring a specific antibiotherapy, often associated with corticosteroid treatment.
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