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在“新冠疫情时期”的 CAR T 细胞治疗的生产和管理:中心与床边方案。

Manufacturing and Management of CAR T-Cell Therapy in "COVID-19's Time": Central Versus Point of Care Proposals.

机构信息

Department of Immunology, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain.

Department of Hematology, Institut Clínic de Malalties Hematològiques i Oncològiques, Hospital Clínic de Barcelona, Barcelona, Spain.

出版信息

Front Immunol. 2020 Oct 15;11:573179. doi: 10.3389/fimmu.2020.573179. eCollection 2020.

Abstract

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the population has affected the supply chains of these life-saving medical products. The aim of this mini-review is to focus on how the COVID-19 pandemic has affected CAR T-cell therapy and taking into consideration the differences between the large-scale centralized productions for the pharmaceutical industry versus product manufacturing in the academic/hospital environment. We also review different aspects of CAR T-cell therapy and our managerial experience of patient selection, resource prioritization and some practical aspects to consider for safe administration. Although hospitals have been forced to change their usual workflows to cope with the saturation of health services by hospitalized patients, we recommend centers to continue offering this potentially curative treatment for patients with relapsed/refractory hematologic malignancies. Consequently, we propose appropriate selection criteria, early intervention to attenuate neurotoxicity or cytokine release syndrome with tocilizumab and prophylactic/preventive strategies to prevent infection. These considerations may apply to other emerging adoptive cell treatments and the corresponding manufacturing processes.

摘要

由严重急性呼吸系统综合症冠状病毒 2 型(SARS-CoV-2)引起的 COVID-19 大流行,对包括嵌合抗原受体(CAR)T 细胞在内的过继细胞疗法的管理产生了重大影响。边境关闭、人员流动减少和人口隔离,影响了这些救命医疗产品的供应链。本篇迷你综述的目的在于聚焦 COVID-19 大流行对 CAR T 细胞疗法的影响,并考虑到大规模集中生产与学术/医院环境中产品制造之间的差异。我们还回顾了 CAR T 细胞疗法的不同方面,以及我们在患者选择、资源优先级和安全管理方面的一些实际考虑的管理经验。尽管医院被迫改变其常规工作流程,以应对住院患者使卫生服务饱和的情况,但我们建议中心继续为复发/难治性血液恶性肿瘤患者提供这种潜在的治愈性治疗。因此,我们提出了适当的选择标准,早期干预以减轻托珠单抗的神经毒性或细胞因子释放综合征,并制定预防感染的策略。这些考虑因素可能适用于其他新兴的过继细胞治疗方法及其相应的制造过程。

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