一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immunotherapy in Lung Cancer: Current Landscape and Future Directions.
Immunotherapy in Lung Cancer: Current Landscape and Future Directions.
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在过去十年中,肺癌治疗经历了重大的范式转变。对肺癌生物学的深入理解促进了众多有效靶向治疗以及免疫治疗的发展。免疫检查点抑制剂(ICIs)在非小细胞肺癌(NSCLC)的治疗中展现出巨大获益,目前已被用作转移性疾病的一线治疗、不可切除局部晚期疾病放化疗后的巩固治疗,以及可切除疾病手术切除和化疗后的辅助治疗。尽管有这些获益,预测哪些患者会对ICIs产生应答仍然困难,且仍需要发现新的免疫治疗预测性生物标志物。此外,肺癌中对ICIs的耐药很常见,原因可能是缺乏应答或初始应答后疾病进展。ICIs在小细胞肺癌(SCLC)治疗中的应用仍限于广泛期疾病的一线治疗联合化疗,对总生存期的影响有限。因此,探索和利用额外靶点以充分获取免疫治疗在肺癌治疗中的全部获益十分重要。在此,我们将总结肺癌免疫治疗的现状,讨论新型靶点,并探索DNA修复缺陷与免疫治疗之间的交叉点。
Over the past decade, lung cancer treatment has undergone a major paradigm shift. A greater understanding of lung cancer biology has led to the development of many effective targeted therapies as well as of immunotherapy.
Immune checkpoint inhibitors (ICIs) have shown tremendous benefit in the treatment of non-small cell lung cancer (NSCLC) and are now being used as first-line therapies in metastatic disease, consolidation therapy following chemoradiation in unresectable locally advanced disease, and adjuvant therapy following surgical resection and chemotherapy in resectable disease. Despite these benefits, predicting who will respond to ICIs has proven to be difficult and there remains a need to discover new predictive immunotherapy biomarkers.
Furthermore, resistance to ICIs in lung cancer is frequent either because of a lack of response or disease progression after an initial response. The utility of ICIs in the treatment of small cell lung cancer (SCLC) remains limited to first-line treatment of extensive stage disease in combination with chemotherapy with modest impact on overall survival. It is thus important to explore and exploit additional targets to reap the full benefits of immunotherapy in the treatment of lung cancer.
Here, we will summarize the current state of immunotherapy in lung cancer, discuss novel targets, and explore the intersection between DNA repair defects and immunotherapy.
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