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.
英文原题:Lung cancer immunotherapy in 2025: where we stand and what comes next?
Lung cancer immunotherapy in 2025: where we stand and what comes next?
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肺癌仍是全球癌症相关死亡的首要原因,其死亡人数超过乳腺癌、结直肠癌和前列腺癌的总和。过去十年,免疫疗法的引入重塑了治疗模式,使这种既往预后极差的疾病有望实现长期生存。免疫检查点抑制剂(ICI)用于非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC),改善了早期、局部晚期及转移性疾病患者的结局。
然而,只有部分患者能获得持久获益,克服耐药、预测疗效、管理毒性和确保公平可及性仍是挑战。本综述全面介绍肺癌免疫治疗的当前进展,讨论肺肿瘤免疫生物学、不同疾病阶段检查点阻断的作用、耐药机制、生物标志物开发及联合治疗策略。文章还深入探讨双特异性抗体、基于CAR和TCR的细胞疗法、自然杀伤(NK)细胞平台、细胞因子激动剂、溶瘤病毒和疫苗等新兴疗法,并评估临床前模型的转化意义、毒性管理以及公平性和可及性问题。
最后,综述提出可能在未来几年重塑肺癌免疫治疗的关键方向。总体而言,这些进展显示治疗正从广泛应用检查点抑制,转向按疾病阶段制定、以生物标志物为依据的多模式免疫疗法,旨在将短暂应答转化为持久缓解并最终实现治愈。
Lung cancer continues to be the leading cause of cancer-related mortality worldwide, accounting for more deaths than breast, colorectal, and prostate cancers combined. Over the past decade, the introduction of immunotherapy has reshaped treatment paradigms, offering hope for long-term survival in a disease historically associated with dismal outcomes.
The incorporation of immune checkpoint inhibitors (ICIs) into the treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) has improved outcomes across early-stage, locally advanced, and metastatic settings.
However, only a fraction of patients derive durable benefit, and challenges remain in overcoming resistance, predicting response, managing toxicity, and ensuring equitable access. This review provides a comprehensive overview of current progress in lung cancer immunotherapy.
It discusses the immunobiology of lung tumors, the role of checkpoint blockade across disease stages, mechanisms of resistance, biomarker development, and combination strategies. Emerging modalities, including bispecific antibodies, CAR- and TCR-based cellular therapies, natural killer (NK) cell platforms, cytokine agonists, oncolytic viruses, and vaccines, are explored in depth.
We also evaluate the translational significance of preclinical models, toxicity management, and issues of equity and accessibility.
Finally, we outline key future directions that may redefine lung cancer immunotherapy in the coming years. Collectively, these advances highlight a transition from broad applications of checkpoint inhibition toward stage-specific, biomarker-driven, and multimodal immunotherapy approaches designed to convert temporary responses into durable remissions and, ultimately, cures.
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