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:Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products.
Pre-treatment with systemic agents for advanced NSCLC elicits changes in the phenotype of autologous T cell therapy products.
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过继T细胞疗法(ACT)的抗肿瘤活性高度依赖过继转移细胞的扩增、持续存在及持续活性。ACT临床研究显示,具有并保持较低分化表型(包括记忆T细胞和前体T细胞)的产品,因扩增能力更强、持续性更佳且可分化为介导抗肿瘤应答的效应子代细胞,因而抗肿瘤疗效更高、患者结局更好。推动T细胞向具有较强持续性和自我更新潜力的记忆型或前体型亚群分化,可增强过继转移T细胞的维持能力,并促进持久抗肿瘤疗效。由于ACT制备成本高昂,患者通常在接受多轮全身治疗后才能获得ACT治疗机会。制备自体ACT药品时必须考虑患者初始T细胞的适应性和亚型组成;这些特征可能随年龄、疾病史及既往抗癌治疗而不同。本研究评估了用于治疗非小细胞肺癌的全身抗癌治疗,对患者基线T细胞表型以及生产完成后基因修饰自体T细胞治疗产品质量和特征的影响。
The antitumor activity of adoptive T cell therapies (ACT) is highly dependent on the expansion, persistence, and continued activity of adoptively transferred cells. Clinical studies using ACTs have revealed that products that possess and maintain less differentiated phenotypes, including memory and precursor T cells, show increased antitumor efficacy and superior patient outcomes owing to their increased expansion, persistence, and ability to differentiate into effector progeny that elicit antitumor responses.
Strategies that drive the differentiation into memory or precursor-type T cell subsets with high potential for persistence and self-renewal will enhance adoptively transferred T cell maintenance and promote durable antitumor efficacy. Because of the high costs associated with ACT manufacturing, ACTs are often only offered to patients after multiple rounds of systemic therapy.
An essential factor to consider in producing autologous ACT medicinal products is the impact of the patient's initial T cell fitness and subtype composition, which will likely differ with age, disease history, and treatment with prior anti-cancer therapies.
This study evaluated the impact of systemic anti-cancer therapy for non-small cell lung cancer treatment on the T cell phenotype of the patient at baseline and the quality and characteristics of the genetically modified autologous T cell therapy product after manufacturing.
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