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:The burden of SARS-CoV-2 in patients receiving chimeric antigen receptor T cell immunotherapy: everything to lose.
The burden of SARS-CoV-2 in patients receiving chimeric antigen receptor T cell immunotherapy: everything to lose.
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在现有观察性研究中,感染 SARS-CoV-2 的 CAR-T 细胞接受者的合并死亡率达 40%。
引言:CAR-T(CAR-T)细胞免疫疗法显著改变了复发/难治性B细胞恶性肿瘤的预后。CAR-T 受者因B细胞缺失而发生免疫抑制,更容易感染呼吸道病毒,且疫苗应答较差。综述范围:本文聚焦B细胞靶向免疫疗法带来的挑战:在致命病毒大流行反复暴发期间,如何处理长期B细胞功能受损。报告仅纳入CAR-T 受者疫苗效果、感染COVID-19后的结局及治疗管理特点相关数据。
我们检索MEDLINE数据库截至2022年3月31日的相关研究。专家观点:现有观察性研究中,感染SARS-CoV-2的CAR-T 受者合并死亡率达40%。
此外,受者的疫苗应答似乎普遍受损(血清转阳率20%,T细胞缓解率50%)。在B细胞耗竭情况下,被动免疫治疗是治疗的基础。康复者血浆疗法已证明是一种高效的根治性治疗,不良事件少。中和性单克隆抗体可用于暴露前预防或早期治疗,但新变异株不断挑战其中和活性。为减少病毒复制,应考虑使用直接抗病毒药物。
INTRODUCTION: Chimeric antigen receptor T (CAR-T) cell immunotherapy has revolutionized the prognosis of refractory or relapsed B-cell malignancies. CAR-T cell recipients have immunosuppression generated by B-cell aplasia, leading to a higher susceptibility to respiratory virus infections and poor response to vaccination. AREAS COVERED: This review focuses on the challenge posed by B-cell targeted immunotherapies: managing long-lasting B-cell impairment during the successive surges of a deadly viral pandemic.
We restricted this report to data regarding vaccine efficacy in CAR-T cell recipients, outcomes after developing COVID-19 and specificities of treatment management.
We searched in MEDLINE database to identify relevant studies until 31 March 2022. EXPERT OPINION: Among available observational studies, the pooled mortality rate reached 40% in CAR-T cell recipients infected by SARS-CoV-2.
Additionally, vaccine responses seem to be widely impaired in recipients (seroconversion 20%, T-cell response 50%). In this setting of B-cell depletion, passive immunotherapy is the backbone of treatment. Convalescent plasma therapy has proven to be a highly effective curative treatment with rare adverse events.
Neutralizing monoclonal antibodies could be used as pre-exposure prophylaxis or early treatment but their neutralizing activity is constantly challenged by new variants. In order to reduce viral replication, direct-acting antiviral drugs should be considered.
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