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:Current Strategies for Extensive Stage Small Cell Lung Cancer Beyond First-line Therapy.
Current Strategies for Extensive Stage Small Cell Lung Cancer Beyond First-line Therapy.
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广泛期小细胞肺癌预后极差,在一线铂类依托泊苷联合方案中加入免疫检查点抑制剂仅能适度改善结局。一旦疾病复发,治疗反应本质上只是短暂的。正在探索的各种策略包括双检查点阻断、BiTE和CAR-T 细胞方法。免疫检查点抑制剂正在与PARP抑制剂联合。目前正在研究的其他方法包括脂质体伊立替康,以及在复发背景下将已知对小细胞肺癌有活性的药物联合,例如新获批的lurbinectedin与多柔比星、紫杉醇、伊立替康或多西他赛联合,或拓扑替康与ATR抑制剂(Berzosertib)联合。替莫唑胺也已与PARP抑制剂联合进行测试。新的抗体或小分子药物偶联物正在积极研究中,基于生物标志物的方法也是如此。通过高通量基因组学、蛋白质组学和甲基化谱分析更好地理解小细胞肺癌疾病生物学,为我们在遏制这一致命疾病的努力中带来了一线希望。文末提供了正在研究的代表性分子靶点表格。
Extensive stage small cell lung cancer carries extremely poor prognosis and adding immune checkpoint inhibitor to platinum etoposide combination in first line only improved outcomes modestly. Once disease recurs, treatment response is only transient in nature. Various strategies that are being explored include dual checkpoint blockade, BiTE and CAR-T cell approaches. Immune checkpoint inhibitors are being combined with PARP inhibitors. Other approaches currently being investigated include liposomal irinotecan and combining known active agents for SCLC in relapsed setting such as newly approved lurbinectedin with doxorubicin, paclitaxel, irinotecan or topotecan with ATR inhibitor (Berzosertib).
Temozolomide has also been tested in combination with a Parp inhibitor. New antibody or small molecule drug conjugates are being actively investigated, so is a biomarker based approach. Better understanding of small cell lung cancer disease biology via high through-put genomic, proteomic and methylation profiling offer glimpse of hope in our efforts to contain this deadly disease. A table of representative molecular targets under investigation is provided in the end.
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